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  • 1.
    Abtahi, Farhad
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. Karolinska Institutet, Sweden.
    Hilderman, Marie
    Bruchfeld, Annette
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. University of Borås, Sweden.
    Janerot-Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. Karolinska Institutet, Sweden.
    Pro-inflammatory Blood Markers and Heart Rate Variability in Apnoea as a Reflection of Basal Vagal ToneManuscript (preprint) (Other academic)
    Abstract [en]

    Pro-inflammatory cytokines play a crucial role in inflammatory response, which istightly regulated by the nervous system to avoid the damage caused by inflammation. There isevidence for a cholinergic anti-inflammatory pathway that includes afferent and efferent vagalnerves that sense the inflammation and stimulate the anti-inflammatory response. Non-functionalanti-inflammatory response might lead to excessive and chronic inflammation e.g., rheumatoidarthritis (RA), inflammatory bowel disease (IBD), and poor outcome. Heart rate variability(HRV) has been proposed as a potential tool to monitor the level of anti-inflammatory activitythrough the monitoring of vagal activity. In this paper, the association of pro-inflammatorymarkers with HRV indices is evaluated. We used a database called “Heart Biomarker Evaluationin Apnea Treatment (HeartBEAT)” that consists of 6±2 hours of Electrocardiogram (ECG)recordings during nocturnal sleep from 318 patients at baseline and 301of them at 3 monthsfollow-up. HRV indices are calculated from ECG recordings of 5-360 minutes. The results showa statistically significant correlation between heart rate (HR) and pro-inflammatory cytokines,independent of duration of ECG analysis. HRV indices e.g., standard deviation of all RRintervals (SDNN) show an inverse relation to the pro-inflammatory cytokines. Longer ECGrecordings show a higher potential to reflect the level of anti-inflammatory response. In light oftheories for the cholinergic anti-inflammatory pathway, a combination of HR and HRV as areflection of basal vagal activity might be a potential prognostic tool for interventional guidance.

  • 2. Barrefelt, Asa
    et al.
    Zhao, Ying
    Larsson, Malin K.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Egri, Gabriella
    Kuiper, Raoul V.
    Hamm, Jorg
    Saghafian, Maryam
    Caidahl, Kenneth
    Brismar, Torkel B.
    Aspelin, Peter
    Heuchel, Rainer
    Muhammed, Mamoun
    Dahne, Lars
    Hassan, Moustapha
    Fluorescence labeled microbubbles for multimodal imaging2015In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 464, no 3, p. 737-742Article in journal (Refereed)
    Abstract [en]

    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.

  • 3. Bassan, Gioia
    et al.
    Larsson, David
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Nordenfur, Tim
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Acquisition of multiple mode shear wave propagation in transversely isotropic medium using dualprobe setup2015Conference paper (Refereed)
  • 4.
    Bennati, Paolo
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Dasu, A.
    Colarieti-Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Lönn, Gustaf
    KTH, School of Technology and Health (STH), Medical Engineering.
    Larsson, David
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Fabbri, A.
    Galasso, M.
    Cinti, M. N.
    Pellegrini, R.
    Pani, R.
    Preliminary study of a new gamma imager for on-line proton range monitoring during proton radiotherapy2017In: Journal of Instrumentation, ISSN 1748-0221, E-ISSN 1748-0221, Vol. 12, no 5, article id C05009Article in journal (Refereed)
    Abstract [en]

    We designed and tested new concept imaging devices, based on a thin scintillating crystal, aimed at the online monitoring of the range of protons in tissue during proton radiotherapy. The proposed crystal can guarantee better spatial resolution and lower sensitivity with respect to a thicker one, at the cost of a coarser energy resolution. Two different samples of thin crystals were coupled to a position sensitive photo multiplier tube read out by 64 independent channels electronics. The detector was equipped with a knife-edge Lead collimator that defined a reasonable field of view of about 10 cm in the target. Geant4 Monte Carlo simulations were used to optimize the design of the experimental setup and assess the accuracy of the results. Experimental measurements were carried out at the Skandion Clinic, the recently opened proton beam facility in Uppsala, Sweden. PMMA and water phantoms studies were performed with a first prototype based on a round 6.0 mm thick Cry019 crystal and with a second detector based on a thinner 5 × 5 cm2, 2.0 mm thick LFS crystal. Phantoms were irradiated with mono-energetic proton beams whose energy was in the range between 110 and 160 MeV. According with the simulations and the experimental data, the detector based on LFS crystal seems able to identify the peak of prompt-gamma radiation and its results are in fair agreement with the expected shift of the proton range as a function of energy. The count rate remains one of the most critical limitations of our system, which was able to cope with only about 20% of the clinical dose rate. Nevertheless, we are confident that our study might provide the basis for developing a new full-functional system.

  • 5.
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Univ Hosp, Sweden.
    Scarce resources call for us to weigh the pros and cons of every single decision2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 8, p. 880-880Article in journal (Other academic)
  • 6.
    Broomé, Michael
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska University Hospital and Karolinska Institutet, Sweden.
    Donker, D. W.
    Individualized real-time clinical decision support to monitor cardiac loading during venoarterial ECMO2016In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 14, no 1Article in journal (Refereed)
    Abstract [en]

    Veno-arterial extracoporeal membrane oxygenation (VA ECMO) is increasingly used for acute and refractory cardiogenic shock. Yet, in clinical practice, monitoring of cardiac loading conditions during VA ECMO can be cumbersome. To this end, we illustrate the validity and clinical applicability of a real-time cardiovascular computer simulation, which allows to integrate hemodynamics, cardiac dimensions and the corresponding degree of VA ECMO support and ventricular loading in individual patients over time.

  • 7.
    Broomé, Michael
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Frenckner, Björn
    Broman, Mikaeö
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Recirculation during veno-venous extra-corporeal membrane oxygenation: a simulation study2015In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, no 1, p. 23-30Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Veno-venous ECMO is indicated in reversible life-threatening respiratory failure without life-threatening circulatory failure. Recirculation of oxygenated blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is difficult to measure. We seek to identify and quantify some of the factors responsible for recirculation in a simulation model and compare with clinical data.

    METHODS:

    A closed-loop real-time simulation model of the cardiovascular system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min with various cannulation sites - 1) right atrium to inferior vena cava, 2) inferior vena cava to right atrium, and 3) superior+inferior vena cava to right atrium. Simulations are compared to data from a retrospective cohort of 11 consecutive adult veno-venous ECMO patients in our department.

    RESULTS:

    Recirculation increases with increasing ECMO-flow, decreases with increasing cardiac output, and is highly dependent on choice of cannulation sites. A more peripheral drainage site decreases recirculation substantially.

    CONCLUSIONS:

    Simulations suggest that recirculation is a significant clinical problem in veno-venous ECMO in agreement with clinical data. Due to the difficulties in measuring recirculation and interpretation of the venous oxygen saturation in the ECMO drainage blood, flow settings and cannula positioning should rather be optimized with help of arterial oxygenation parameters. Simulation may be useful in quantification and understanding of recirculation in VV-ECMO.

  • 8.
    Bälter, Olle
    et al.
    KTH, School of Computer Science and Communication (CSC), Media Technology and Interaction Design, MID.
    Colareti Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Kann, Viggo
    KTH, School of Computer Science and Communication (CSC), Theoretical Computer Science, TCS.
    Svedin, Maria
    KTH, School of Computer Science and Communication (CSC), Media Technology and Interaction Design, MID.
    Lärstrategier på längden och tvären2015In: 5:e Utvecklingskonferensen för Sveriges ingenjörsutbildningar, Uppsala universitet, Uppsala universitet, 2015Conference paper (Refereed)
    Abstract [sv]

    Studiestrategier påverkar vad studenter får ut av sin utbildning. Vi har genomfört enkätstudier (ASSIST och RSPQ) för att mäta strategierna hos civilingenjörsstudenter på två olika program (Datateknik respektive Medicinsk teknik) på KTH. Resultaten visar att för denna tämligen homogena studentgrupp finns det inga större skillnader mellan årskurser eller program, men studenter med ytinriktad studiestrategi kommer efter eller hoppar av i större utsträckning än andra. Eftersom det åtminstone går att normalisera studiestrategier är det viktigt att arbeta för att normen är konstruktiv, det vill säga minska inslaget av ytinriktade strategier. De bägge instrumenten korrelerar runt 0,5 med varandra och enstaka frågor går att ifrågasätta, varför tolkningar av enstaka mätningar bör göras med försiktighet. 

  • 9. Campo, A. B.
    et al.
    Dirckx, J. J.
    Widman, Erik
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Waz, A. T.
    Dudzik, G.
    Abramski, K. M.
    Application of a new four-channel vibrometer for determination of atherosclerosis: Further advances towards a handheld device2016In: 2016 IEEE International Symposium on Medical Measurements and Applications, MeMeA 2016 - Proceedings, Institute of Electrical and Electronics Engineers (IEEE), 2016Conference paper (Refereed)
    Abstract [en]

    Cardiovascular diseases (CD) are the leading cause of death worldwide and their prevalence is expected to rise. Important in the etiology of CD is the stiffening of the large arteries (arteriosclerosis) and plaque formation (atherosclerosis) in the common carotid artery (CCA). Increasing evidence shows that both arteriosclerosis and atherosclerosis can be detected by assessing pulse wave velocity (PWV) in the CCA, and several techniques focus on the detection of PWV in this structure. In previous studies, laser Doppler vibrometry (LDV) was proposed as an approach to detect arterial stiffness. In the present work, a compact four-channel LDV system is introduced for PWV detection. Four phantom arteries were assessed mimicking real life cardiovascular pathologies. Due to the high sensitivity and the increased spatial and temporal resolution of the LDV system, PWV could be assessed, and even local changes in phantom architecture could be detected. The system could potentially be used to detect arteriosclerosis and arterial plaque during cardiovascular screening.

  • 10.
    Chowdhury, Manish
    et al.
    KTH, School of Technology and Health (STH).
    Jörgens, Daniel
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization.
    Wang, Chunliang
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization. KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Smedby, Örjan
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization.
    Moreno, Rodrigo
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization.
    Segmentation of Cortical Bone using Fast Level Sets2017In: MEDICAL IMAGING 2017: IMAGE PROCESSING / [ed] Styner, MA Angelini, ED, SPIE - International Society for Optical Engineering, 2017, article id UNSP 1013327Conference paper (Refereed)
    Abstract [en]

    Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

  • 11.
    Colarieti-Tosti, Massimiliano
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Brooks, M. S. S.
    Eriksson, O.
    Approximate Molecular and Crystal Field Excitation Energies Derived from Density Functional TheoryManuscript (preprint) (Other academic)
  • 12.
    da Silva, Cristina
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institute, Stockholm, Sweden .
    Sahlén, Anders
    Winter, Reidar
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska University Hospital, Sweden.
    Bäck, Magnus
    Ruck, Andreas
    Settergren, Magnus
    Manouras, Aristomenis
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Department of Cardiology, Karolinska University Hospital, Huddinge, Sweden .
    Shahgaldi, Kambiz
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Department of Cardiology, Karolinska University Hospital, Huddinge, Sweden .
    Hemodynamic outcomes of transcatheter aortic valve implantation with the CoreValve system: an early assessment2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 3, p. 216-222Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Transcatheter aortic valve implantation (TAVI) is an established method for the treatment of high-risk patients with aortic stenosis (AS). The beneficial effects of TAVI in cardiac hemodynamics have been described in recent studies, but those investigations were mostly performed after an interval of more than 6 months following aortic valve implantation. The aim of this study is to investigate the acute and short-term alterations in hemodynamic conditions using the echocardiography outcomes in patients undergoing TAVI. Methods and Results: A total of 60 patients (26 males, 34 females; age 84·7 ± 5·8) who underwent TAVI with CoreValve system were included in the study. Echocardiography was performed before hospital discharge and at 3 months follow-up. As expected, TAVI was associated with an immediate significant improvement in aortic valve area (AVA) (from 0·64 ± 0·16 cm2 to 1·67 ± 0·41 cm2, P-value<0·001) and mean gradient (from 51·9 ± 15·4 mmHg to 8·8 ± 3·8 mmHg, P-value<0·001). At 3-month follow-up, systolic LV function was augmented (EF: 50 ± 14% to 54 ± 11%, P-value = 0·024). Left ventricle (LV) mass and left atrium (LA) volume were significantly reduced (LV mass index from 126·5 ± 30·5 g m-2 to 102·4 ± 32·4 g m-2; LA index from 42·9 ± 17·3 ml m-2 to 33·6 ± 10·6 ml m-2; P-value<0·001 for both). Furthermore, a decrement in systolic pulmonary artery pressure (SPAP) from 47·5 ± 13·5 mmHg to 42·5 ± 11·2 mmHg, P-value = 0·02 was also observed. Despite the high incidence of paravalvular regurgitation (PVR) (80%), most of the patients presented mild or trace PVR and no significant progress of the regurgitation grade was seen after 3 months. Conclusion: This study demonstrates that the beneficial effects of TAVI in cardiac function and hemodynamics occur already after a short period following aortic valve implantation.

  • 13.
    Faridi, M. A.
    et al.
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ramachandraiah, H.
    KTH, School of Biotechnology (BIO).
    Iranmanesh, I. S.
    KTH, School of Biotechnology (BIO). KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Microbubble assisted cell sorting by acoustophoresis2016In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, Chemical and Biological Microsystems Society , 2016, p. 1677-1678Conference paper (Refereed)
    Abstract [en]

    Polymer shelled gas microbubbles (MBs) are used to sort cells in a microfluidic chip under acoustic standing waves (SW). When particles are subjected to SW based on their acoustic contrast factor (ACF) they migrate to nodes (positive contrast factor particles; PACP) or antinodes (negative acoustic contrast particles; NACP)[1]. We have bounded functionalized MBs with cells such that, they can be selectively migrated to antinodes under SW and sorted from unbounded cell both in no flow and flow conditions. Here we demonstrate acoustic mediated microbubble tagged cell sorting with 75% efficiency.

  • 14.
    Faridi, Muhammad Asim
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. mafaridi@kth.se.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Iranmanesh, Ida Sadat
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    MicroBubble Activated Acoustic Cell Sorting: BAACSIn: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781Article in journal (Refereed)
    Abstract [en]

    Acoustophoresis, the ability to acoustically manipulate particles and cells inside a microfluidic channel, is a critical enabling technology for cell-sorting applications. However, one of the major impediments for routine use of acoustophoresis at clinical laboratory has been the reliance on the inherent physical properties of cells for separation. Here, we present a microfluidic-based microBubble-Activated Acoustic Cell Sorting (BAACS) method that rely on the specific binding of target cells to microbubbles conjugated with specific antibodies on their surface for continuous cell separation using ultrasonic standing wave. In acoustophoresis, cells being positive acoustic contrast particles migrate to pressure nodes. On the contrary we show that air-filled polymer-shelled microbubbles being strong negative acoustic contrast particles migrate to pressure antinodes at acoustic pressure amplitudes as low as 60 kPa. As a proof of principle, using the BAACS strategy, we demonstrate the separation of cancer cell line in a suspension with better than 75% efficiency. Moreover, 100% of the microbubble-cell conjugates migrated to the anti-node. Hence a better upstream affinity-capture has the potential to provide higher sorting efficiency. The BAACS technique may potentially provide a simplistic approach for similar sized selective isolation of cells, and is suited for applications in point of care.

  • 15.
    Faridi, Muhammad Asim
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. mafaridi@kth.se.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Iranmanesh, Ida Sadat
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    MicroBubble Activated Acoustic Cell Sorting: BAACS2017In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 19, no 2Article in journal (Refereed)
    Abstract [en]

    Acoustophoresis, the ability to acoustically manipulate particles and cells inside a microfluidic channel, is a critical enabling technology for cell-sorting applications. However, one of the major impediments for routine use of acoustophoresis at clinical laboratory has been the reliance on the inherent physical properties of cells for separation. Here, we present a microfluidic-based microBubble-Activated Acoustic Cell Sorting (BAACS) method that rely on the specific binding of target cells to microbubbles conjugated with specific antibodies on their surface for continuous cell separation using ultrasonic standing wave. In acoustophoresis, cells being positive acoustic contrast particles migrate to pressure nodes. On the contrary we show that air-filled polymer-shelled microbubbles being strong negative acoustic contrast particles migrate to pressure antinodes at acoustic pressure amplitudes as low as 60 kPa. As a proof of principle, using the BAACS strategy, we demonstrate the separation of cancer cell line in a suspension with better than 75% efficiency. Moreover, 100% of the microbubble-cell conjugates migrated to the anti-node. Hence a better upstream affinity-capture has the potential to provide higher sorting efficiency. The BAACS technique may potentially provide a simplistic approach for similar sized selective isolation of cells, and is suited for applications in point of care.

  • 16.
    Frank A, Flachskampf
    et al.
    Uppsala Universitet, Institutionen för Medicinska Vetenskaper, Akademiska sjukhuset.
    Mattias, Mårtensson
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    How should tissue Doppler tracings be measured?2014In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 15, no 7, p. 828-829Article in journal (Refereed)
  • 17. Gharehbaghi, Arash
    et al.
    Borga, Magnus
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Ask, Per
    A novel method for discrimination between innocent and pathological heart murmurs2015In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 7, p. 674-682Article in journal (Refereed)
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

  • 18.
    Gharehbaghi, Arash
    et al.
    Linkoping Univ, Dept Biomed Engn, Physiol Measurements, Linkoping, Sweden..
    Ekman, Inger
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Dept Clin Physiol, Linkoping, Sweden..
    Ask, Per
    Linkoping Univ, Dept Biomed Engn, Physiol Measurements, Linkoping, Sweden..
    Nylander, Eva
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Dept Clin Physiol, Linkoping, Sweden.;Linkoping Univ, Ctr Med Image Sci & Visualizat, Linkoping, Sweden..
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Med Imaging & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Med Technol, Stockholm, Sweden.;KTH Royal Inst Technol, Sch Technol & Hlth, Stockholm, Sweden..
    Assessment of aortic valve stenosis severity using intelligent phonocardiography2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 198, p. 58-60Article in journal (Refereed)
  • 19.
    Hamid Muhammed, Hamed
    et al.
    KTH, School of Technology and Health (STH), Health Systems Engineering, Systems Safety and Management.
    Kothapalli, Satya V.V.N
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Using Ultrasonic Spectrometry to Estimate the Stability of a Dental Implant Phantom2013In: Engineering, ISSN 1947-3931, E-ISSN 1947-394X, Vol. 5, p. 570-574Article in journal (Refereed)
    Abstract [en]

    A challenging problem in dental implant surgery is to evaluate the stability of the implant. In this simulation study, an experimental phantom is used to represent a jawbone with a dental implant. It is made of a little pool filled with soft-tissue equivalent material and a disc of fresh Oakwood with a metal screw. Varying levels of contact between screw and wood are simulated by screwing in or out the screw. Initially, the screw is screwed in and fixed firmly in wood. Thereafter, the screw is screwed out, a half turn each time, to increase the gap gradually between wood and screw. Pulse-echo ultrasound is used and the power spectra of the received echo-signals are computed. These spectra are normalized then analyzed by using the partial least squares method to estimate the corresponding implant stiffness grade in terms of number of turns when beginning from the initial tight-screw state then screwing out the screw. A coefficient of determination R2 of 96.4% and a mean absolute error of ±0.23 turns are achieved when comparing real and estimated values of stiffness grades, indicating the efficiency of this approach.

  • 20. Hashemi, N.
    et al.
    Samad, B. A.
    Hedman, A.
    Brodin, Lars Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Alam, M.
    Feasibility of Myocardial Performance Index for Evaluation of Left Ventricular Function during Dobutamine Stress Echocardiography before and after Coronary Artery Bypass Grafting2014In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 31, no 8, p. 989-995Article in journal (Refereed)
    Abstract [en]

    Aims: Myocardial performance index (MPI) is a measure of combined systolic and diastolic myocardial function. In patients with coronary artery disease (CAD) an increase in MPI is consistent with myocardial dysfunction. The objectives of this study were to characterize the changes in MPI after coronary artery bypass graft (CABG) at rest and at peak dobutamine stress echocardiography (DSE). Methods and Results: Thirty-six patients diagnosed with CAD and accepted for CABG were studied by standard echocardiography and DSE 1 month prior and 3 month after CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction (EF; 42.7 ± 8%) and wall-motion score index (WMSI; 1.1 ± 0.2) were impaired at rest as well as at peak DSE (EF; 49.2 ± 9 and WMSI 1.4 ± 0.2). MPI was prolonged both at rest (0.61 ± 0.13) and at peak DSE (0.78 ± 0.16). After CABG, EF and WMSI did not improve at rest (43.7 ± 8% and 1.1 ± 0.2, respectively). On the other hand, MPI improved substantially both at rest (0.45 ± 0.08; P < 0.001) and at peak DSE (0.56 ± 0.1; P < 0.001). At peak DSE an improvement of EF (54.2 ± 9; P < 0.05) and WMSI (1.1 ± 0.16; P < 0.001) was seen as well. Conclusion: Myocardial performance index shows significant improvement after CABG in patients with CAD both at rest and peak DSE and appears to be a sensitive measure of myocardial function.

  • 21.
    Härmark, Johan
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Structural Biotechnology.
    Larsson, Malin K.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Razuvajev, Anton
    Koeck, Philip JB
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Structural Biotechnology.
    Paradossi, Gaio
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Caidahl, Kenneth
    Hebert, Hans
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Structural Biotechnology.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Investigation of the elimination process of a multimodal polymer-shelled contrast agent in rats using ultrasound and transmission electron microscopy2015In: Biomedical Spectroscopy and Imaging, ISSN 2212-8794, Vol. 4, no 1, p. 81-93Article in journal (Refereed)
    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.

  • 22.
    Johnson, Jonas
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Manouras, Aristomenis
    KTH, School of Technology and Health (STH), Medical Engineering. Karolinska Institute, Sweden.
    Bergholm, Fredrik
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Brodin, Lars Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Agewall, S.
    Henareh, L.
    The early diastolic myocardial velocity: A marker of increased risk in patients with coronary heart disease2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 5, p. 389-396Article in journal (Refereed)
    Abstract [en]

    Objective: Tissue Doppler imaging (TDI) is a promising echocardiographic modality allowing quantification of myocardial performance. However, the prognostic potential of TDI in patients with acute myocardial infarction (AMI) is not yet investigated. We sought to explore the ability of TDI in identifying patients at risk for new cardiovascular events after AMI. Methods: One hundred and nineteen patients with AMI were recruited prospectively (mean age 61 years; range 32-81 years of age). Patients with diabetes mellitus (DM) were excluded. Echocardiography was performed 3-12 months after AMI. Two-dimensional (2-D) and TDI variables were recorded. The patients were followed during a mean period of 4·6 years (range 1-8 years). The primary end-point was defined as any of the following: death from any cause, non-fatal reinfarction or stroke, unstable angina pectoris, congestive heart failure requiring hospitalization and coronary revascularization procedure. Results: Thirty patients had some form of cardiovascular events during follow-up. Seven patients had cardiovascular death, 13 patients had reinfarction and four patients had a stroke. New angina or unstable angina was recorded in 21 patients. Of these patients, 13 underwent percutaneous coronary angioplasty (PCI) or coronary artery bypass grafting (CABG). The early diastolic myocardial velocity (Em) emerged as the only echocardiographic variable that offered a clear differentiation between patients that presented with new cardiovascular (CV) events as compared to the corresponding group without any CV events at follow-up (P&lt;0·05). In multivariate statistical analysis and after adjustment for age, sex, total cholesterol, body mass index (BMI) and other baseline characteristics, Em remained as independent predictors of CV events (HR, 1·18, 95% CI, 1·02-1·36; P&lt;0·05). However, none of the investigated variables evolved as an independent predictor of cardiovascular morbidity and mortality. Conclusion: Em appears to be a sensitive echocardiographic index in identifying non-diabetic patients with AMI at risk of new cardiovascular events.

  • 23.
    Josefsson, Leila
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Larsson, Malin K.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institute, Sweden.
    Emmer, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Analysis of polyvinyl alcohol microbubbles in human blood plasma using capillary electrophoresis2016In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 39, no 8, p. 1551-1558Article in journal (Refereed)
    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.

  • 24.
    Kothapalli, Satya V.V.N.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Nano-Engineered Contrast Agents: Toward Multimodal Imaging and Acoustophoresis2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diagnostic ultrasound (US) is safer, quicker and cheaper than other diagnostic imaging modalities. Over the past two decades, the applications of US imaging has been widened due to the development of injectable, compressible and encapsulated microbubbles (MBs) that provide an opportunity to improve conventional echocardiographic imaging, blood flow assessment and molecular imaging. The encapsulating material is manufactured by different biocompatible materials such as proteins, lipids or polymers. In current research, researchers modify the encapsulated shell with the help of advanced molecular chemistry techniques to load them with dyes (for fluorescent imaging), nanoparticles and radioisotopes (for multimodal imaging) or functional ligands or therapeutic gases (for local drug delivery). The echogenicity and the radial oscillation of MBs is the result of their compressibility, which undoubtedly varies with the encapsulated shell characteristics such as rigidity or elasticity.

    In this thesis, we present acoustic properties of novel type of polyvinyl alcohol (PVA)-shelled microbubble (PVA-MB) that was further modified with superparamagnetic iron oxide nanoparticles (SPIONs) to work as a dual-modal contrast agent for magnetic resonance (MR) imaging along with US imaging. Apparently, the shell modification changes their mechanical characteristics, which affects their acoustic properties. The overall objective of the thesis is to investigate the acoustic properties of modified and unmodified PVA-MBs at different ultrasound parameters.

    The acoustic and mechanical characterization of SPIONs modified PVA-MBs revealed that the acoustical response depends on the SPION inclusion strategy. However they retain the same structural characteristics after the modification. The modified MBs with SPIONs included on the surface of the PVA shell exhibit a soft-shelled behavior and produce a higher echogenicity than the MBs with the SPIONs inside the PVA shell. The fracturing mechanism of the unmodified PVA-MBs was identified to be different from the other fracturing mechanisms of conventional MBs. With the interaction of high-pressure bursts, the air gas core is squeezed out through small punctures in the PVA shell. During the fracturing, the PVA-MBs exhibit asymmetric (other modes) oscillations, resulting in sub- and ultra-harmonic generation. Exploiting the US imaging at the other modes of the oscillation of the PVA-MBs would provide an opportunity to visualize very low concentrations of (down to single) PVA-MBs. We further introduced the PVA-MBs along with particles mimicking red blood cells in an acoustic standing-wave field to observe the acoustic radiation force effect. We observed that the compressible PVA-MBs drawn toward pressure antinode while the solid blood phantoms moved toward the pressure node. This acoustic separation method (acoustophoresis) could be an efficient tool for studying the bioclearance of the PVA-MBs in the body, either by collecting blood samples (in-vitro) or by using the extracorporeal medical procedure (ex-vivo) at different organs.

    Overall, this work contributes significant feedback for chemists (to optimize the nanoparticle inclusion) and imaging groups (to develop new imaging sequences), and the positive findings pave new paths and provide triggers to engage in further research. 

  • 25.
    Kothapalli, Satya V.V.N.
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Paradossi, Gaio
    Diapartimento di Chimica, Università di Roma Tor Vergata.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Investigation of Polymer-Shelled Microbubble Motions in AcoustophoresisManuscript (preprint) (Other academic)
    Abstract [en]

    The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a redblood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acousticstanding-wave field and to compare the corresponding movements of solid polymer microbeads. Theexperimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with aresonance frequency of about 2.8 MHz. The microfluidic channel consists of a rectangular chamberwith a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one fullwave ultrasound of a standing-wave pattern with two pressure nodes at4w and43w and threeantinodes at 0,2w , and w. The peak-to-peak amplitude of the electrical potential over the PZT wasvaried between 1 and 10 volts. From Gor’kov’s potential equation, the acoustic contrast factor, Φ, forthe polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstratethat the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes.This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similarto what has been described for other acoustic contrast particles with a negative Φ. First, primaryradiation forces dragged the polymer-shelled microbubbles into proximity with each other at thepressure antinode planes. Then, secondary radiation forces caused them to aggregate at different spotsalong the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter thanthat for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelledmicrobubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1 volt.In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negativeacoustic contrast factor particles and thus can be trapped at the antinode plane and thereby seperatedfrom solid particles, such as cells. This phenomenon could be utilized in exploring future applications,such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.

  • 26.
    Kothapalli, Veera Venkata Satya Naray
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Daeichin, Verya
    Department of Biomedical Engineering, Thoraxcenter, Erasmus MC,.
    Mastik, Frits
    Department of Biomedical Engineering, Thoraxcenter, Erasmus MC.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Paradossi, Gaio
    Diapartimento di Chimica, Università di Roma Tor Vergata.
    de Jong, N.
    Department of Biomedical Engineering, Thoraxcenter, Erasmus MC.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: An acoustic characterization and optical visualization2014In: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, ISSN 0885-3010, E-ISSN 1525-8955, Vol. 62, no 3, p. 451-462, article id 7055440Article in journal (Refereed)
    Abstract [en]

    This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.

  • 27.
    Kothapalli, Veeravenkata S.
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Oddo, Letizia
    Paradossi, Gaio
    Brodin, Lars- Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Inst, Sweden.
    Assessment of the Viscoelastic and Oscillation Properties of a Nano-engineered Multimodality Contrast Agent2014In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 40, no 10, p. 2476-2487Article in journal (Refereed)
    Abstract [en]

    Combinations of microbubbles (MBs) and superparamagnetic iron oxide nanoparticles (SPIONs) are used to fabricate dual contrast agents for ultrasound and MRI. This study examines the viscoelastic and oscillation characteristics of two MB types that are manufactured with SPIONs and either anchored chemically on the surface (MBs-chem) or physically embedded (MBs-phys) into a polymer shell. A linearized Church model was employed to simultaneously fit attenuation coefficients and phase velocity spectra that were acquired experimentally. The model predicted lower viscoelastic modulus values, undamped resonance frequencies and total damping ratios for MBs-chem. MBs-chem had a resonance frequency of approximately 13 MHz and a damping ratio of approximately 0.9; thus, MBs-chem can potentially be used as a conventional ultrasound contrast agent with the combined functionality of MRI detection. In contrast, MBs-phys had a resonance frequency and damping of 28 MHz and 1.2, respectively, and requires further modification of clinically available contrast pulse sequences to be visualized.

  • 28.
    Larsson, David
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Spuhler, Jeannette H.
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz).
    Nordenfur, Tim
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Hoffman, Johan
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz).
    Colarieti-Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Gao, Hang
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Patient-specific flow simulation of the left ventricle from 4D echocardiography - feasibility and robustness evaluation2015In: 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS), IEEE , 2015Conference paper (Refereed)
    Abstract [en]

    In recent years, computational fluid dynamics (CFD) simulations on in-silico models of the heart have provided a valuable insight into cardiac hemodynamic behaviour. However, so far most models have been either based on simplified geometries or on imaging acquisitions with relatively low temporal resolution. It has been suggested that models based entirely on subject-specific ultrasonic images should be used to capture transient flow changes. Therefore, the aim of this study is to present a pathway from routine 4D echocardiography to a patient-specific flow simulation of the left ventricle (LV), evaluating the model robustness and clinical feasibility. The created pathway consisted of initial LV segmentation and mitral/aortic valve positioning, being subsequently used as input for the CFD simulations (based on solving the Navier-Stokes equation using an Arbitrary Lagrangian-Eulerian approach). The output consisted of 4D blood flow velocities and relative pressures in the entire LV. On five subjects, the model robustness was evaluated with regards to variations in singular boundary conditions. The clinical feasibility of the output was compared to clinical PW Doppler measurements and, as a proof-of-concept, synthetic contrast enhanced ultrasound images were simulated on the flow field using the COLE-method. Results indicated a relatively robust model, with variations in regional flow of approximately 5.1/6.2% and 9.7/7.0% for healthy and pathological subject respectively (end diastole/end systole). Furthermore, showing similar behaviour to clinical Doppler measurements the technique serves as a promising tool for future clinical investigations. Additionally, the ability of simulating synthetic ultrasound images further underlines the applicability of the pathway, being potentially useful in studies on improved echocardiographic image analysis.

  • 29.
    Larsson, David
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Spuhler, Jeannette H.
    Petersson, Sven
    Nordenfur, Tim
    Hoffman, Johan
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz).
    Colarieti-Tosti, Massimiliano
    Winter, Reidar
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Multimodal validation of patient-specific intraventricular flow simulations from 4D echocardiography2016In: 2016 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS), IEEE conference proceedings, 2016Conference paper (Refereed)
    Abstract [en]

    The combination of refined medical imaging techniques and computational fluid dynamics (CFD) models has enabled the study of complex flow behavior on a highly regional level. Recently, we have developed a platform for patient-specific CFD modelling of blood flow in the left ventricle (LV), with input data and required boundary conditions acquired from 4D echocardiography. The platform robustness has been evaluated with respect to input variable variations, but for any clinical implementation model flow validation is essential. Therefore, the aim of this study is to evaluate the accuracy of the patient-specific CFD model against multimodal image-based flow measurements. For the validation, 4D echocardiography was acquired from two healthy subjects, from which LV velocity fields were simulated. In-vivo flows from the same two subjects were then acquired by pulsed wave (PW) Doppler imaging over both LV-valves, and by cine phase-contract magnetic resonance imaging (PC-MRI) at eight defined anatomical planes in the LV. By fusing PC-MRI and the ultrasound acquisitions using a three-chamber alignment algorithm, simulated and measured flows were quantitatively compared. General flow pattern correspondence was observed, with a mean error of 1.4 cm/s and root mean square deviation of 5.7 cm/s for all measured PC-MRI LV-planes. For the PW-Doppler comparison, a mean error of 3.6 cm/s was reported. Overall, the following work represents a validation of the proposed patient-specific CFD platform, and the agreement with clinical data highlight the potential for future clinical use of the models.

  • 30.
    Larsson, David
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Insitutet, Sweden.
    Spühler, Jeannette
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Günyeli, E.
    Weinkauf, Tino
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Hoffman, Johan
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Colarieti-Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Winter, R.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Estimation of left ventricular blood flow parameters: Clinical application of patient-specific CFD simulations from 4D echocardiography2017In: Medical Imaging 2017: Ultrasonic Imaging and Tomography, SPIE - International Society for Optical Engineering, 2017, Vol. 10139, article id 101390LConference paper (Refereed)
    Abstract [en]

    Echocardiography is the most commonly used image modality in cardiology, assessing several aspects of cardiac viability. The importance of cardiac hemodynamics and 4D blood flow motion has recently been highlighted, however such assessment is still difficult using routine echo-imaging. Instead, combining imaging with computational fluid dynamics (CFD)-simulations has proven valuable, but only a few models have been applied clinically. In the following, patient-specific CFD-simulations from transthoracic dobutamin stress echocardiography have been used to analyze the left ventricular 4D blood flow in three subjects: two with normal and one with reduced left ventricular function. At each stress level, 4D-images were acquired using a GE Vivid E9 (4VD, 1.7MHz/3.3MHz) and velocity fields simulated using a presented pathway involving endocardial segmentation, valve position identification, and solution of the incompressible Navier-Stokes equation. Flow components defined as direct flow, delayed ejection flow, retained inflow, and residual volume were calculated by particle tracing using 4th-order Runge-Kutta integration. Additionally, systolic and diastolic average velocity fields were generated. Results indicated no major changes in average velocity fields for any of the subjects. For the two subjects with normal left ventricular function, increased direct flow, decreased delayed ejection flow, constant retained inflow, and a considerable drop in residual volume was seen at increasing stress. Contrary, for the subject with reduced left ventricular function, the delayed ejection flow increased whilst the retained inflow decreased at increasing stress levels. This feasibility study represents one of the first clinical applications of an echo-based patient-specific CFD-model at elevated stress levels, and highlights the potential of using echo-based models to capture highly transient flow events, as well as the ability of using simulation tools to study clinically complex phenomena. With larger patient studies planned for the future, and with the possibility of adding more anatomical features into the model framework, the current work demonstrates the potential of patient-specific CFD-models as a tool for quantifying 4D blood flow in the heart.

  • 31.
    Larsson, David
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. KTH.
    Spühler, Jeannette Hiromi
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Petersson, Sven
    Karolinska Universitetssjukhuset.
    Nordenfur, Tim
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Colarieti-Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Hoffman, Johan
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Winter, Reidar
    Karolinska Institutet.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Patient-Specific Left Ventricular Flow Simulations From Transthoracic Echocardiography: Robustness Evaluation and Validation Against Ultrasound Doppler and Magnetic Resonance Imaging2017In: IEEE Transactions on Medical Imaging, ISSN 0278-0062, E-ISSN 1558-254X, Vol. 36, no 11, p. 2261-2275Article in journal (Refereed)
    Abstract [en]

    The combination of medical imaging with computational fluid dynamics (CFD) has enabled the study of 3D blood flow on a patient-specificlevel. However, with models based on gated high-resolution data, the study of transient flows, and any model implementation into routine cardiac care, is challenging. The present paper presents a novel pathway for patient-specific CFD modelling of the left ventricle (LV), using 4D transthoracic echocardiography (TTE) as input modality. To evaluate the clinical usability, two sub-studies were performed. First, a robustness evaluation was performed where repeated models with alternating input variables were generated for 6 subjects and changes in simulated output quantified. Second, a validation study was carried out where the pathway accuracy was evaluated against pulsed-wave Doppler (100 subjects), and 2D through-plane phase-contrast magnetic resonance imaging measurements over 7 intraventricular planes (6 subjects). The robustness evaluation indicated a model deviation of <12%, with highest regional and temporal deviations at apical segments and at peak systole, respectively. The validation study showed an error of < 11% (velocities < 10 cm/s) for all subjects, with no significant regional or temporal differences observed. With the patient-specific pathway shown to provide robust output with high accuracy, and with the pathway dependent only on 4DTTE, the method has a high potential to be used within future clinical studies on 3D intraventricular flowpatterns. To this, future model developments in the form of e.g. anatomically accurate LV valves may further enhance the clinical value of the simulations.

  • 32.
    Larsson, Malin
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Toward increased applicability of ultrasound contrast agents2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

  • 33.
    Larsson, Malin
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Da Silva, Cristina
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital.
    Gunyeli, Elif
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital.
    Akebat Bin Ilami, Ali
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital.
    Szummer, Karolina
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital.
    Winter, Reidar
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    The potential clinical value of contrast-enhanced echocardiography beyond current recommendationsManuscript (preprint) (Other academic)
  • 34.
    Larsson, Malin K.
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Nowak, Greg
    Paradossi, Gaio
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Caidahl, Kenneth
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent2014In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 12, p. 24-Article in journal (Refereed)
    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.

  • 35.
    Larsson, Matilda
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. KU Leuven, Campus Gasthuisberg OandN1, Belgium.
    Heyde, Brecht
    Kremer, Florence
    Brodin, Lars-Ake
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    D'hooge, Jan
    Ultrasound speckle tracking for radial, longitudinal and circumferential strain estimation of the carotid artery: An in vitro validation via sonomicrometry using clinical and high-frequency ultrasound2014In: Ultrasonics, ISSN 0041-624X, E-ISSN 1874-9968, Vol. 56, p. 399-408Article in journal (Refereed)
    Abstract [en]

    Ultrasound speckle tracking for carotid strain assessment has in the past decade gained interest in studies of arterial stiffness and cardiovascular diseases. The aim of this study was to validate and directly contrast carotid strain assessment by speckle tracking applied on clinical and high-frequency ultrasound images in vitro. Four polyvinyl alcohol phantoms mimicking the carotid artery were constructed with different mechanical properties and connected to a pump generating carotid flow profiles. Gray-scale ultrasound long-and short-axis images of the phantoms were obtained using a standard clinical ultrasound system, Vivid 7 (GE Healthcare, Horten, Norway) and a high-frequency ultrasound system, Vevo 2100 (FUJIFILM, VisualSonics, Toronto, Canada) with linear-array transducers (12L / MS250). Radial, longitudinal and circumferential strains were estimated using an in-house speckle tracking algorithm and compared with reference strain acquired by sonomicrometry. Overall, the estimated strain corresponded well with the reference strain. The correlation between estimated peak strain in clinical ultrasound images and reference strain was 0.91 (p < 0.001) for radial strain, 0.73 (p < 0.001) for longitudinal strain and 0.90 (p < 0.001) for circumferential strain and for high-frequency ultrasound images 0.95 (p < 0.001) for radial strain, 0.93 (p < 0.001) for longitudinal strain and 0.90 (p < 0.001) for circumferential strain. A significant larger bias and root mean square error was found for circumferential strain estimation on clinical ultrasound images compared to high frequency ultrasound images, but no significant difference in bias and root mean square error was found for radial and longitudinal strain when comparing estimation on clinical and high-frequency ultrasound images. The agreement between sonomicrometry and speckle tracking demonstrates that carotid strain assessment by ultrasound speckle tracking is feasible.

  • 36.
    Larsson, Matilda
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Kremer, F.
    Heyde, B.
    Brodin, Lars Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    D'hooge, J.
    Ultrasound-based speckle tracking for 3D Strain estimation of the Arterial wall - An experimental validation study in a tissue mimicking phantom2011Conference paper (Refereed)
    Abstract [en]

    Arterial stiffness is an important risk factor for cardiovascular disease. As such, ultrasound-based methods have been proposed to assess arterial strain as a measure of stiffness. The aim of the current study was to validate our recently proposed speckle tracking (ST) algorithm to estimate the in-plane wall strain tensor in an experimental setup. Three polyvinyl alcohol phantoms mimicking the carotid artery were constructed with different mechanical properties (2, 3 and 4 freeze-thaw cycles). The phantoms were connected to a pump, programmed to generate carotid flow profiles at peak flows of 7, 14, 21, 28 and 35 ml/s. Long and short-axis ultrasound images were obtained using a Vivid7 Dimension system. Radial, longitudinal and circumferential strains were estimated using the ST algorithm (kernel size: 2.7λx2λ, normalized cross-correlation; spline inter-polation for subsample motion estimation; 40% window overlap). Sonomicrometry was used to acquire reference values of strain in the phantoms. Good agreement was found between the estimated radial, longitudinal and circumferential strain and the acquired reference strain. The correlation between estimated mean peak strain values and reference peak strain values was r = 0.92 (p < 0.001) for radial strain, r = 0.72 (p = 0.006) for longitudinal strain and r = 0.91 (p < 0.001) for circumferential strain.

  • 37.
    Larsson, Matilda
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. University of Leuven, Belgium .
    Verbrugghe, Peter
    Smoljkić, Marija
    Verhoeven, Jelle
    Heyde, Brecht
    Famaey, Nele
    Herijgers, Paul
    D'hooge, Jan
    Strain assessment in the carotid artery wall using ultrasound speckle tracking: validation in a sheep model.2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 3, p. 1107-Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to validate carotid artery strain assessment in-vivo using ultrasound speckle tracking. The left carotid artery of five sheep was exposed and sonomicrometry crystals were sutured onto the artery wall to obtain reference strain. Ultrasound imaging was performed at baseline and stress, followed by strain estimation using an in-house speckle tracking algorithm tuned for vascular applications. The correlation between estimated and reference strain was r = 0.95 (p < 0.001) and r = 0.87 (p < 0.01) for longitudinal and circumferential strain, respectively. Moreover, acceptable limits of agreement were found in Bland-Altman analysis (longitudinally: -0.15 to 0.42%, circumferentially: -0.54 to 0.50%), which demonstrates the feasibility of estimating carotid artery strain using ultrasound speckle tracking. However, further studies are needed to test the algorithm on human in-vivo data and to investigate its potential to detect subclinical cardiovascular disease and characterize atherosclerotic plaques.

  • 38.
    Lindberg, Frida
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Mårtensson, Mattias
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Aesthetic ultrasound devices: Current state of knowledge and suggested measurement set-up for characterization of exposure2013Report (Other academic)
    Abstract [en]

    This report concerns the ultrasound devices used for the aesthetic purposes of body contouring and fat reduction (ablation of adipose tissue). Such devices have recently become more frequent on the Swedish market. These ultrasound devices are currently not medically regulated in Sweden and little is known about their safety and potentially harmful exposure when using them.

    This report aims to provide relevant information about present guidelines and scientific results in the area, a survey of the Swedish market and also recommendations on how to characterize the ultrasound emitted by these devices. This information provides an important basis for possible future regulatory actions.

    All aesthetic ultrasound devices found on the Swedish market use low-frequency non-thermal ultrasound. These types of devices (with one exception) have not yet been studied in peer-reviewed publications and the technical specifications from the suppliers are often incomplete. Consequently, there is a need to evaluate the devices in order to gain adequate knowledge about possible risks associated with their use.

    Ultrasound exposure should be characterized by its frequency and acoustic pressure. It has not been fully investigated whether the mathematical equation for the mechanical index is valid for the low frequencies used by aesthetic ultrasound equipment on the Swedish market. In this report, two different hydrophone measurement set-ups for characterization of ultrasound exposure are proposed. The most common reason behind adverse events or exposure of non-target tissue regions is most likely handling errors by the operator. Hence, only characterization of the ultrasound field does not necessarily imply the safe use of aesthetic ultrasound devices.

    It is recommended that the Swedish Radiation Safety Authority and the Swedish Medical Products Agency discuss their respective future responsibility and how aesthetic ultrasound devices should be regulated.

  • 39.
    Lindberg, Frida
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Mårtensson, Mattias
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Grönlund, Christer
    Medicinsk Teknik - FoU, Umeå Univeristet.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Evaluation of ultrasound Tissue Velocity Imaging: a phantom study of velocity estimation in skeletal muscle low-level contractions2013In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 13, no 1, p. 16-Article in journal (Refereed)
    Abstract [en]

    Background: Tissue Velocity Imaging (TVI) is an ultrasound based technique used for quantitative analysis of the cardiac function and has earlier been evaluated according to myocardial velocities. Recent years several studies have reported applying TVI in the analysis of skeletal muscles. Skeletal tissue velocities can be very low. In particular, when performing isometric contractions or contractions of low force level the velocities may be much lower compared to the myocardial tissue velocities. Methods: In this study TVI was evaluated for estimation of tissue velocities below the typical myocardial velocities. An in-house phantom was used to see how different PRF-settings affected the accuracy of the velocity estimations. Results: With phantom peak velocity at 0.03 cm/s the error ranged from 31% up to 313% with the different PRF-settings in this study. For the peak velocities at 0.17 cm/s and 0.26 cm/s there was no difference in error with tested PFR settings, it is kept approximately around 20%. Conclusions: The results from the present study showed that the PRF setting did not seem to affect the accuracy of the velocity estimation at tissue velocities above 0.17 cm/s. However at lower velocities (0.03 cm/s) the setting was crucial for the accuracy. The PRF should therefore preferable be reduced when the method is applied in low-level muscle contraction.

  • 40.
    Liu, Xuejin
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Characterization and Energy Calibration of a Silicon-Strip Detector for Photon-Counting Spectral Computed Tomography2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Multibin photon-counting x-ray detectors are promising candidates to be applied in next generation computed tomography (CT), whereby energy information from a broad x-ray spectrum can be extracted and properly used for improving image quality and correspondingly reducing radiation dose. A silicon-strip detector has been developed for spectral CT, which operates in photon-counting mode and allows pulse-height discrimination with 8 adjustable energy bins.

    Critical characteristics, energy resolution and count-rate performance, of the detector are evaluated. An absolute energy resolution (E) from 1.5 keV to 1.9 keV with increasing x-ray energy from 40 keV to 120 keV is found. Pulse pileup degrades the energy resolution by 0.4 keV when increasing the input count rate from zero to 100 Mcps mm−2, while charge sharing shows negligible effect. A near linear relationship between the input and output count rates is observed up to 90 Mcps mm−2 in a clinical CT environment. In addition, no saturation effect appears for the maximally achieved photon flux of 485 Mphotons s−1 mm−2 with a count rate loss of 30%.

    The detector is energy calibrated in terms of gain and offset with the aid of monoenergetic x rays. The gain variation among channels is below 4%, whereas the variation of offsets is on the order of 1 keV. In order to do the energy calibration in a routinely available way, a method that makes use of the broad x-ray spectrum instead of using monoenergetic x rays is proposed. It is based on a regression analysis that adjusts a modelled spectrum of deposited energies to a measured pulse-height spectrum. Application of this method shows high potential to be applied in an existing CT scanner with an uncertainty of a calibrated threshold between 0.1 and 0.2 keV.

    The energy-calibration method is further used in the development of a spectral response model of the detector. This model is used to accurately bin-wise predict the response of each detector channel, which is validated by two application examples. First, the model is used in combination with the inhomogeneity compensation method to eliminate ring artefacts in CT images. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. Additionally, the contrast agent concentrations are reconstructed with more than 94% accuracy.

  • 41. Lund, Mikael
    et al.
    von Dobeln, Gabriella Alexandersson
    Nilsson, Magnus
    Winter, Reidar
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Lundell, Lars
    Tsai, Jon A.
    Kalman, Sigridur
    Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction: a prospective cohort pilot study within a randomized clinical trial2015In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 10, article id 16Article in journal (Refereed)
    Abstract [en]

    Background: Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Methods: Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. Results: 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p = 0.10). Conclusions: Neoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function.

  • 42.
    Maksuti, Elira
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Imaging and modeling the cardiovascular system2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system.  Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease.

    The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal.

    In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing.

    The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms.

  • 43.
    Maksuti, Elira
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institute, Sweden .
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institute, Sweden .
    Modelling the heart with the atrioventricular plane as a piston unit2015In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 1, p. 87-92Article in journal (Refereed)
    Abstract [en]

    Medical imaging and clinical studies have proven that the heart pumps by means of minor outer volume changes and back-and-forth longitudinal movements in the atrioventricular (AV) region. The magnitude of AV-plane displacement has also shown to be a reliable index for diagnosis of heart failure. Despite this, AV-plane displacement is usually omitted from cardiovascular modelling. We present a lumped-parameter cardiac model in which the heart is described as a displacement pump with the AV plane functioning as a piston unit (AV piston). This unit is constructed of different upper and lower areas analogous with the difference in the atrial and ventricular cross-sections. The model output reproduces normal physiology, with a left ventricular pressure in the range of 8-130 mmHg, an atrial pressure of approximatly 9 mmHg, and an arterial pressure change between 75 mmHg and 130 mmHg. In addition, the model reproduces the direction of the main systolic and diastolic movements of the AV piston with realistic velocity magnitude (similar to 10 cm/s). Moreover, changes in the simulated systolic ventricular-contraction force influence diastolic filling, emphasizing the coupling between cardiac systolic and diastolic functions. The agreement between the simulation and normal physiology highlights the importance of myocardial longitudinal movements and of atrioventricular interactions in cardiac pumping.

  • 44.
    Maksuti, Elira
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Carlsson, Marcus
    Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Clinical Physiology, Lund, Sweden..
    Arheden, Håkan
    Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Clinical Physiology, Lund, Sweden..
    Kovács, Sándor J.
    Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA..
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Ugander, Martin
    Department of Clinical Physiology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden..
    Hydraulic forces contribute to left ventricular diastolic filling2016Manuscript (preprint) (Other academic)
    Abstract [en]

    Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was the same order of magnitude as the peak driving force of LV (1-3N vs 5-10N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the resulting hydraulic forces, should be considered when characterizing diastolic function and dysfunction. 

  • 45.
    Maksuti, Elira
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Inst, Sweden.
    Westerhof, Nico
    Westerhof, Berend E.
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Inst, Sweden.
    Stergiopulos, Nikos
    Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging: A Simulation Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0157493Article in journal (Refereed)
    Abstract [en]

    During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.

  • 46.
    Maksuti, Elira
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Widman, Erik
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Larsson, David
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Urban, Matthew W.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    ARTERIAL STIFFNESS ESTIMATION BY SHEAR WAVE ELASTOGRAPHY: VALIDATION IN PHANTOMS WITH MECHANICAL TESTING2016In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 42, no 1, p. 308-321Article in journal (Refereed)
    Abstract [en]

    Arterial stiffness is an independent risk factor found to correlate with a wide range of cardiovascular diseases. It has been suggested that shear wave elastography (SWE) can be used to quantitatively measure local arterial shear modulus, but an accuracy assessment of the technique for arterial applications has not yet been performed. In this study, the influence of confined geometry on shear modulus estimation, by both group and phase velocity analysis, was assessed, and the accuracy of SWE in comparison with mechanical testing was measured in nine pressurized arterial phantoms. The results indicated that group velocity with an infinite medium assumption estimated shear modulus values incorrectly in comparison with mechanical testing in arterial phantoms (6.7 +/- 0.0 kPa from group velocity and 30.5 +/- 0.4 kPa from mechanical testing). To the contrary, SWE measurements based on phase velocity analysis (30.6 +/- 3.2 kPa) were in good agreement with mechanical testing, with a relative error between the two techniques of 8.8 +/- 6.0% in the shear modulus range evaluated (40-100 kPa). SWE by phase velocity analysis was validated to accurately measure stiffness in arterial phantoms.

  • 47. Mattsson, C. M.
    et al.
    Lind, Britta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Enqvist, J. K.
    Mårtensson, Mattias
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Ekblom, B.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    No evidence of cardiac fatigue in tissue velocity curves at rest after 6 days of ultra-endurance exercise2010In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, p. 304-305Article in journal (Refereed)
  • 48. Medrano-Gracia, Pau
    et al.
    Ormiston, John
    Webster, Mark
    Beier, Susann
    Ellis, Chris
    Wang, Chunliang
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization. KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Smedby, Örjan
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization.
    Young, Alistair
    Cowan, Brett
    A Study of Coronary Bifurcation Shape in a Normal Population2017In: Journal of Cardiovascular Translational Research, ISSN 1937-5387, E-ISSN 1937-5395, Vol. 10, no 1, p. 82-90Article in journal (Refereed)
    Abstract [en]

    During percutaneous coronary intervention, stents are placed in narrowings of the arteries to restore normal blood flow. Despite improvements in stent design, deployment techniques and drug-eluting coatings, restenosis and stent thrombosis remain a significant problem. Population stent design based on statistical shape analysis may improve clinical outcomes. Computed tomographic (CT) coronary angiography scans from 211 patients with a zero calcium score, no stenoses and no intermediate artery, were used to create statistical shape models of 446 major coronary artery bifurcations (left main, first diagonal and obtuse marginal and right coronary crux). Coherent point drift was used for registration. Principal component analysis shape scores were tested against clinical risk factors, quantifying the importance of recognised shape features in intervention including size, angles and curvature. Significant differences were found in (1) vessel size and bifurcation angle between the left main and other bifurcations; (2) inlet and curvature angle between the right coronary crux and other bifurcations; and (3) size and bifurcation angle by sex. Hypertension, smoking history and diabetes did not appear to have an association with shape. Physiological diameter laws were compared, with the Huo-Kassab model having the best fit. Bifurcation coronary anatomy can be partitioned into clinically meaningful modes of variation showing significant shape differences. A computational atlas of normal coronary bifurcation shape, where disease is common, may aid in the design of new stents and deployment techniques, by providing data for bench-top testing and computational modelling of blood flow and vessel wall mechanics.

  • 49. Monnier, Andreas
    et al.
    Larsson, Helena
    Djupsjobacka, Mats
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Ang, Bjorn O.
    Musculoskeletal pain and limitations in work ability in Swedish marines: a cross-sectional survey of prevalence and associated factors2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 10, article id e007943Article in journal (Refereed)
    Abstract [en]

    Objectives To estimate the prevalence of self-rated musculoskeletal pain and pain limiting work ability in Swedish Armed Forces (SAF) marines, and to study factors potentially associated with pain limiting work ability for the most prevalent pain regions reported. Design Population-based, cross-sectional survey. Participants There were 272 SAF marines from the main marine battalion in Sweden included in the study. Outcomes Self-assessed musculoskeletal pain and pain limiting the marines' work ability within a 6-month period, as obtained from structured questionnaires. The association of individual, health and work-related factors with musculoskeletal pain limiting work ability was systematically regressed with multiple logistic models, estimating OR and 95% CI. Results Musculoskeletal pain and pain limiting work ability were most common in the back, at 46% and 20%, and lower extremities at 51% and 29%, respectively. Physical training 1day/week (OR 5.3, 95% CI 1.7 to 16.8); body height 1.80m (OR 5.0, 95% CI 1.6 to 15.1) and 1.86m (OR 4.4, 95% CI 1.4 to 14.1); computer work 1/4 of the working day (OR 3.2, 95% CI 1.0 to 10.0) and 1/2 (OR 3.3, 95% CI 1.1 to 10.1) of the working day were independently associated with back pain limiting work ability. None of the studied variables emerged significantly associated with such pain for the lower extremities. Conclusions Our findings show that musculoskeletal pain and resultant limitations in work ability are common in SAF marines. Low frequency of physical training emerged independently associated with back pain limiting work ability. This suggests that marines performing physical training 1day per week or less are suitable candidates for further medical evaluation and secondary preventive actions. While also associated, body height and computer work need further exploration as underlying mechanisms for back pain limiting work ability. Further prospective studies are necessary to clarify the direction of causality.

  • 50.
    Mårtensson, Mattias
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Evaluation of tissue Doppler-based velocity and deformation imaging: a phantom study of ultrasound systems.2011In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Vol. 12, no 6, p. 467-476Article in journal (Refereed)
    Abstract [en]

    AIMS: The objective of this study was to test the accuracy and diagnostic interchangeability of tissue Doppler-based displacement, velocity, strain, and strain rate measurements in commercially used ultrasound (US) systems. METHODS AND RESULTS: Using an in-house made phantom, four different US scanner models were evaluated. Two different scanners of the same model were tested, and one scanner acquisition was tested twice with two generations of the same workstation giving six test results in total. The scanners were in active clinical use and are subject to regular maintenance checks. There were three displacement and four velocity results that stood out from the rest and could be regarded as accurate and interchangeable. Among the deformation measurements, three acceptable strain results were found while there were no acceptable strain rate results. Furthermore, the study showed that measurements from scanners of the same model, same acquisition post-processed on different workstations and repeated measurements from the same scanner, can yield disparate results. CONCLUSION: Measurements that are accurate and of interchangeable use can be found for displacement and velocity measurements, but are less likely to be found for strain and strain rate measurements. It is strongly recommended that the ability of each individual US scanner to measure displacement, velocity, strain, and strain rate is evaluated before it is introduced into clinical practice, and it must always be evaluated together with the workstation the scanner is intended to be used in conjunction with.

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