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  • 1. Affatato, S.
    et al.
    Leardini, W.
    Jedenmalm, Anneli
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Ruggeri, O.
    Toni, A.
    Larger diameter bearings reduce wear in metal-on-metal hip implants2007In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 456, p. 153-158Article in journal (Refereed)
    Abstract [en]

    Metal-on-metal hip arthroplasty has the longest clinical history of all total arthroplasties. We asked whether large diameter femoral heads would result in less wear than those with small diameters. We also asked if there is a threshold diameter that ensures good wear behavior. We tested three batches of cast high-carbon cobalt-chromium-molybdenum hip implants (28 mm, 36 min, and 54 min diameters) in a hip simulator for 5 million cycles. We used bovine serum as lubricant and weighed the samples at regular intervals during testing. The 28-mm configuration had almost twice the wear of the 54-mm configuration, but we observed no difference between the 36-mm and the 54-mm configurations. The similarity in the wear performances of the larger configurations supports the presence of a threshold diameter that ensures good wear behavior.

  • 2. Aitken, Candice L.
    et al.
    Gorniak, Richard J. T.
    New York University.
    Kramer, Elissa L.
    New York University.
    Noz, Marilyn E.
    New York University.
    Farrell, Eward J.
    IBM Research.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments, Teleinformatics.
    Reddy, David P.
    Comparison of three methods used for fusion of SPECT-CT images of liver matastases1998In: Fusion98, International Conference on Multisource-Mulltisensor Information Fusion / [ed] Hamid R. Arabnia and Dongping (Daniel) Zhu, CSREA Press , 1998, p. 435-442Conference paper (Refereed)
    Abstract [en]

    We compare three methods for fusing SPECT-CT images: ImageMatch - an automatic three-dimensional/two-dimensional method developed by Focus Imaging; IBM Visualization Data Explorer - a three-diemensional interactive method developed by Internation Business Machines, Inc.; and qsh - an interactive three-dimensional/two-dimensional method developed at New York University. While many fusion methods have proved successful for registering brain images, most methods have been less successful for thoracic and abdominal images. We use images of liver metastases obtained with a radiolabeled breast tumor-directed antibody to illustrate the strengths and weakness of the methods reviewed. The images used are typical clinical images from eigth patients. We conclude that an optimal image fusion program should combine the strengths of each of the methods reviewed.

  • 3. Aitken, Candice L.
    et al.
    Mahmoud, Faaiza
    McGuinness, Georgeann
    Kramer, Elissa L.
    Maguire, Gerald Q. Jr.
    KTH, Superseded Departments, Microelectronics and Information Technology, IMIT.
    Noz, Marilyn E.
    New York University.
    Tumor localization and image registration of F-18FDG coincidence detection scans with computed tomographic scans2002In: Clinical Nuclear Medicine, ISSN 0363-9762, E-ISSN 1536-0229, Vol. 27, no 4, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to determine the feasibility of registering routine clinical F-18 fluorodeoxyglucose (FDG) coincidence detection (CD) scans with computed tomographic (CT) scans for radiation treatment planning and case management. Methods: F-18 FDG CD and chest CT scans, performed in 10 randomly selected patients with confirmed or possible adenocarcinoma of the lung, were evaluated. The quality of the matches was verified by comparisons of the center-to-center distance between a region of interest (ROI) manually drawn on the CT slice and warped onto the CD slice with an ROI drawn manually directly on the CD slice. In addition, the overlap between the two ROIs was calculated. Results: All 10 F-18 FDG CD and CT scans were registered with good superimposition of soft tissue density on increased radionuclide activity. The center-to-center distance between the ROIs ranged from 0.29 mm to 8.08 mm, with an average center-to-center distance of 3.89 mm 2.42 mm (0.69 pixels +/- 0.34 pixels). The ROI overlap ranged from 77% to 99%, with an average of 90% +/- 5.6%. Conclusions: Although the use of F-18 FDG CD shows great promise for the identification of tumors, it shares the same drawbacks as those associated with radiolabeled monoclonal antibody SPECT and ligand-based positron emission tomographic scans in that anatomic markers are limited. This study shows that image registration is feasible and may improve the clinical relevance of CD images.

  • 4.
    Aitken, Candice L.
    et al.
    New York University.
    McGuinness, Georgeann
    New York University.
    Siddiqui, Faaiza
    New York University.
    Ton, Anthony
    New York University.
    Kramer, Elissa L
    New York University.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments, Teleinformatics.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Tumor localization and image registration of 18-FDG SPECT scans with CT scans1999In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 40, no 5, p. 290P-291PArticle in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The aim of this study was to determine the feasibility of registering routine clinical F-18 fluorodeoxyglucose (FDG) coincidence detection (CD) scans with computed tomographic (CT) scans for radiation treatment planning and case management.

    METHODS:

    F-18 FDG CD and chest CT scans, performed in 10 randomly selected patients with confirmed or possible adenocarcinoma of the lung, were evaluated. The quality of the matches was verified by comparisons of the center-to-center distance between a region of interest (ROI) manually drawn on the CT slice and warped onto the CD slice with an ROI drawn manually directly on the CD slice. In addition, the overlap between the two ROIs was calculated.

    RESULTS:

    All 10 F-18 FDG CD and CT scans were registered with good superimposition of soft tissue density on increased radionuclide activity. The center-to-center distance between the ROIs ranged from 0.29 mm to 8.08 mm, with an average center-to-center distance of 3.89 mm +/- 2.42 mm (0.69 pixels +/- 0.34 pixels). The ROI overlap ranged from 77% to 99%, with an average of 90% +/- 5.6%.

    CONCLUSIONS:

    Although the use of F-18 FDG CD shows great promise for the identification of tumors, it shares the same drawbacks as those associated with radiolabeled monoclonal antibody SPECT and ligand-based positron emission tomographic scans in that anatomic markers are limited. This study shows that image registration is feasible and may improve the clinical relevance of CD images.

  • 5.
    Akkus, Zeynettin
    et al.
    KTH. Department of Medical Physics, University Hospitals of Leicester, NHS Trust, Leicester, UK.
    Ramnarine, K. V.
    Dynamic assessment of carotid plaque motion2010In: Ultrasound, ISSN 1742-271X, Vol. 18, no 3, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Assessment of dynamic plaque behaviour may help identify vulnerable carotid plaque before rupture and hence has potential clinical value for screening patients at risk of stroke. The aim of this study was to develop non-invasive ultrasound methods for quantifying dynamic plaque and vessel wall behaviour and assess their potential clinical utility. Ultrasound data from the carotid arteries of one normal subject and four patients with atherosclerotic disease were acquired using a 10 MHz linear array transducer recording raw RF/IQ data at a frame rate up to 80 Hz for 3-6 seconds. Image reconstruction and processing was performed using Matlab. Speckle tracking techniques were developed to characterize: (1) intraplaque deformation; and (2) plaque surface and vessel wall motion. Speckle tracking techniques were able to measure the range of intraplaque tissue deformation (-1.3 to 1.7 mm), plaque surface displacement (0.2-0.7 mm) and vessel wall radial strain (0.02-0.13) throughout the cardiac cycle. The feasibility of using an intraplaque deformation parameter, based on the deformation of a square template, is demonstrated. Speckle tracking techniques can be used to assess dynamic carotid plaque behaviour. Further work is required to evaluate how best to quantify biomechanical behaviour to help predict plaque rupture and hence improve risk stratification models for stroke.

  • 6.
    Alcala, Yvonne
    et al.
    New York Medical College .
    Olivecrona, Henrik
    Karolinska.
    Olivecrona, Lotta
    Karolinska.
    Noz, Marilyn E.
    New York University.
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Microelectronics and Information Technology, IMIT.
    Zeleznik, Michael P.
    Sollerman, Christer
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Qualifying CT for wrist arthroplasty: Extending techniques for total hip arthroplasty to total wrist arthroplasty2005In: Medical Imaging 2005: Image Processing, Pt 1-3 / [ed] Fitzpatrick, JM; Reinhardt, JM, SPIE - The International Sooceity for Optical Engineeering , 2005, Vol. 5747, p. 1155-1164Conference paper (Refereed)
    Abstract [en]

    The purpose of this study was to extend previous work to detect migration of total wrist arthroplasty non-invasively, and with greater accuracy. Two human cadaverous arms, each with a cemented total wrist implant, were used in this study. In one of the arms, I mm tantalum balls were implanted, six in the carpal bones and five in the radius. Five CT scans of each arm were acquired, changing the position of the arm each time to mimic different positions patients might take on repeated examinations. Registration of CT volume data sets was performed using an extensively validated, 3D semi-automatic volume fusion tool in which co-homologous point pairs (landmarks) are chosen on each volume to be registered. Three sets of ten cases each were obtained by placing landmarks on 1) bone only (using only arm one), 2) tantalum implants only, and 3) bone and tantalum implants (both using only arm two). The accuracy of the match was assessed visually in 2D and 3D, and numerically by calculating the distance difference between the actual position of the transformed landmarks and their ideal position (i.e., the reference landmark positions). All cases were matched visually within one width of cortical bone and numerically within one half CT voxel (0.32 mm, p = 0.05). This method matched only the bone/arm and not the prosthetic component per se, thus making it possible to detect prosthetic movement and wear. This method was clinically used for one patient with pain. Loosening of the carpal prosthetic component was accurately detected and this was confirmed at surgery.

  • 7. Alkharusi, Amira
    et al.
    Yu, Shengze
    KTH, School of Biotechnology (BIO).
    Landazuri, Natalia
    Zadjali, Fahad
    Davodi, Belghis
    Nystrom, Thomas
    Gräslund, Torbjörn
    KTH, School of Biotechnology (BIO), Protein Technology.
    Rahbar, Afsar
    Norstedt, Gunnar
    Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 48, p. 79558-79569Article in journal (Refereed)
    Abstract [en]

    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.

  • 8. Altai, M.
    et al.
    Honarvar, H.
    Wallberg, H.
    Strand, J.
    Varasteh, Z.
    Orlova, A.
    Dunas, F.
    Sandstrom, M.
    Rosestedt, M.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with Re-1882013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, p. S219-S220Article in journal (Other academic)
  • 9. Altai, M.
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Sandström, M.
    Boschetti, F.
    Orlova, A.
    Tolmachev, V.
    Evaluation of a maleimido derivative of NODAGA for site-specific In-111-labeling of Affibody molecules2011In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 38, p. S146-S146Article in journal (Other academic)
  • 10. Altai, M.
    et al.
    Strand, J.
    Rosik, Daniel
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Selvaraju, R.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Orlova, A.
    Tolmachev, V.
    Comparative evaluation of anti-HER2 affibody molecules labeled with 68Ga and 111In using maleimido derivatives of DOTA and NODAGA.2012In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, p. S299-S299Article in journal (Refereed)
  • 11. Altai, M.
    et al.
    Wallberg, H.
    Honarvar, H.
    Strand, J.
    Orlova, A.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Varasteh, Z.
    Sandström, M.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Re-188-Z(HER2: V2), a promising targeting agent against HER2-expressing tumors: in vitro and in vivo assessment2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, p. S119-S119Article in journal (Other academic)
  • 12. Altai, M.
    et al.
    Westerlund, Kristina
    KTH, School of Biotechnology (BIO), Protein Technology.
    Velletta, J.
    Mitran, B.
    Honarvar, H.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and 177Lu labeling2017In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 54, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Introduction We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA–PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide 177Lu. We also studied the biodistribution profile of 177Lu-HP2 in mice, and evaluated pretargeting with 177Lu-HP2 in vitro and in vivo. Methods The biodistribution profile of 177Lu-HP2 was evaluated in NMRI mice and compared to the previously studied 111In-HP2. Pretargeting using 177Lu-HP2 was studied in vitro using the HER2-expressing cell lines BT‐474 and SKOV-3, and in vivo in mice bearing SKOV-3 xenografts. Results and conclusion Using an optimized production protocol for ZHER2:342-SR-HP1 the ligation time was reduced from 15 h to 30 min, and the yield increased from 45% to 70%. 177Lu-labeled HP2 binds specifically in vitro to BT474 and SKOV-3 cells pre-treated with ZHER2:342-SR-HP1. 177Lu-HP2 was shown to have a more rapid blood clearance compared to 111In-HP2 in NMRI mice, and the measured radioactivity in blood was 0.22 ± 0.1 and 0.68 ± 0.07%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i. In contrast, no significant difference in kidney uptake was observed (4.47 ± 1.17 and 3.94 ± 0.58%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i.). Co-injection with either Gelofusine or lysine significantly reduced the kidney uptake for 177Lu-HP2 (1.0 ± 0.1 and 1.6 ± 0.2, respectively, vs. 2.97 ± 0.87%ID/g in controls at 4 h p.i.). 177Lu-HP2 accumulated in SKOV-3 xenografts in BALB/C nu/nu mice when administered after injection of ZHER2:342-SR-HP1. Without pre-injection of ZHER2:342-SR-HP1, the uptake of 177Lu-HP2 was about 90-fold lower in tumor (0.23 ± 0.08 vs. 20.7 ± 3.5%ID/g). The tumor-to-kidney radioactivity accumulation ratio was almost 5-fold higher in the group of mice pre-injected with ZHER2:342-SR-HP1. In conclusion, 177Lu-HP2 was shown to be a promising secondary agent for affibody-mediated tumor pretargeting in vivo.

  • 13. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Sandström, Mattias
    Boschetti, Frederic
    Orlova, Anna
    Tolmachev, Vladimir
    Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA2012In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, no 4, p. 518-529Article in journal (Refereed)
    Abstract [en]

    Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.

  • 14. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tsourma, Maria
    Mitran, Bogdan
    Honarvar, Hadis
    Robillard, Marc
    Rossin, Raffaella
    ten Hoeve, Wolter
    Lubberink, Mark
    Orlova, Anna
    Karlström, Amelie Eriksson
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, Vladimir
    Feasibility of Affibody-Based Bioorthogonal Chemistry Mediated Radionuclide Pretargeting2016In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 3, p. 431-436Article in journal (Refereed)
    Abstract [en]

    Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of Affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal reabsorption of Affibody molecules prevents the use of residualizing radiometals, including several promising low-energy (beta- and alpha-emitters, for radionuclide therapy. We tested a hypothesis that Affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys. Methods: TCO was conjugated to the anti-human epidermal growth factor receptor 2 (HER2) Affibody molecule Z(2395). DOTA-tetrazine was labeled with In-111 and Lu-177. In vitro pretargeting was studied in HER2-expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts. Results: I-125-Z(2395)-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 +/- 16 pM. In-111-tetrazine bound specifically and selectively to Z(2325)-TCO pretreated cells. In vivo studies demonstrated HER2-specific I-125-Z(2395)-TCO accumulation in xenografts. TCO-mediated In-111-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z(2395)-TCO. At 1 h after injection, the tumor uptake of In-111-tetrazine and Lu-177-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of In-111 in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pre-targeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy.

  • 15. Altai, Mohamed
    et al.
    Wållberg, Helena
    KTH, School of Biotechnology (BIO), Protein Technology.
    Honarvar, Hadis
    Strand, Joanna
    Orlova, Anna
    Varasteh, Zohreh
    Sandström, Mattias
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Larsson, Erik
    Strand, Sven-Erik
    Lubberink, Mark
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology. Uppsala University, Sweden.
    Tolmachev, Vladimir
    Re-188-Z(HER2:V2), a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment2014In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 11, p. 1842-1848Article in journal (Refereed)
    Abstract [en]

    Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of Tc-99m-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated Z(HER2:V2)) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate Re-188-Z(HER2:v2) as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors. Methods: Z(HER2:V2) was labeled with Re-188 using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment. Results: Binding of Re-188-Z(HER2:V2) to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 +/- 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 +/- 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 +/- 2, 12 +/- 2, 5 +/- 2, and 1.8 +/- 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 +/- 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that Re-188-Z(HER2:v2) would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible. Conclusion: (188)ReZ(HER2:v2) can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.

  • 16.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI (closed 20111231).
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Lind, Bengt K.
    Karolinska Institute, Department of Medical Radiation Physics.
    Maguire, Gerald Q. Jr.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS.
    Will haptic feedback speed up medical imaging? An application to radiation treatment planning2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    Haptic technology enables us to incorporate the sense of touch into computer applications, providing an additional input/output channel. The purpose of this study was to examine if haptic feedback can help physicians and other practitioners to interact with medical imaging and treatment planning systems. A haptic application for outlining target areas (a key task in radiation therapy treatment planning) was implemented and then evaluated via a controlled experiment with ten subjects. Even though the sample size was small, and the application only a prototype, results showed that haptic feedback can significantly increase (p0.05) the speed of outlining target volumes and organs at risk. No significant differences were found regarding precision or perceived usability. This promising result warrants further development of a full haptic application for this task. Improvements to the usability of the application as well as to the forces generated have been implemented and an experiment with more subjects is planned.

  • 17.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI (closed 20111231).
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI (closed 20111231).
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS.
    Lind, Bengt K.
    Karolinska Institute, Medical Radiation Physics.
    The value of haptic feedback in medical imaging and treatment planning2006In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 81, p. 1277-Article in journal (Refereed)
  • 18.
    Andersson, Ken G.
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Oroujeni, Maryam
    Garousi, Javad
    Mitran, Bogdan
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Orlova, Anna
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, Vladimir
    Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with Tc-99m using a peptide-based cysteine-containing chelator2016In: International Journal of Oncology, ISSN 1019-6439, Vol. 49, no 6, p. 2285-2293Article in journal (Refereed)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets. The anti-EGFR ZEGFR:2377 affibody molecule is a potential imaging probe for EGFR detection. The use of the generator-produced radionuclide Tc-99m should facilitate clinical translation of an imaging probe due to its low price, availability and favorable dosimetry of the radionuclide. In the present study, we evaluated feasibility of ZEGFR:2377 labeling with Tc-99m using a peptide-based cysteine-containing chelator expressed at the C-terminus of ZEGFR:2377. The label was stable in vitro under cysteine challenge. In addition, Tc-99m-ZEGFR:2377 was capable of specific binding to EGFR-expressing cells with high affinity (274 pM). Studies in BALB/C nu/nu mice bearing A431 xenografts demonstrated that Tc-99m-ZEGFR:2377 accumulates in tumors in an EGFR-specific manner. The tumor uptake values were 3.6 1 and 2.5 0.4% ID/g at 3 and 24 h after injection, respectively. The corresponding tumor-to-blood ratios were 1.8 0.4 and 8 3. The xenografts were clearly visualized at both time-points. This study demonstrated the potential of Tc-99m-labeled ZEGFR:2377 for imaging of EGFR in vivo.

  • 19.
    Andersson, Ken G.
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Varasteh, Z.
    Rosenstedt, M.
    Rosestedt, M.
    Malm, M.
    KTH.
    Sandström, M.
    KTH.
    Tolmachev, V.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Orlova, A.
    111In-labeled NOTA-conjugated Affibody molecules for visualization of HER3 expression in malignant tumors2014In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, p. S311-S311Article in journal (Other academic)
  • 20. Andersson, Malin
    et al.
    Jägervall, Karl
    Eriksson, Per
    Persson, Anders
    Granerus, Göran
    Wang, Chunliang
    Linköping Univ, Sweden.
    Smedby, Örjan
    Linköping Univ, Sweden.
    How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance2015In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 15, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. Methods: Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. Results: A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82-0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists' visual assessments on CTA and MRA were 0.90 (0.82-0.98) and 0.91 (0.83-0.99) respectively. None of the differences were statistically significant. Conclusions: No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with fuzzy connectedness segmentation. Further studies are required to definitely identify the optimal measurement approach.

  • 21. Andersson, Thord
    et al.
    Romu, Thobias
    Karlsson, Anette
    Norén, Bengt
    Forsgren, Mikael F
    Smedby, Örjan
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization. Linköping University.
    Kechagias, Stergios
    Almer, Sven
    Lundberg, Peter
    Borga, Magnus
    Leinhard, Olof Dahlqvist
    Consistent intensity inhomogeneity correction in water-fat MRI2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 2Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities

    METHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.

    RESULTS: CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint⁡≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).

    CONCLUSION: CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type.

  • 22. Andrade, Pedro Amarante
    et al.
    Wistbacka, Greta
    Larsson, Hans
    Sodersten, Maria
    Hammarberg, Britta
    Simberg, Susanna
    Svec, Jan G.
    Granqvist, Svante
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine. Karolinska Institutet, Sweden.
    The Flow and Pressure Relationships in Different Tubes Commonly Used for Semi-occluded Vocal Tract Exercises2016In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, no 1, p. 36-41Article in journal (Refereed)
    Abstract [en]

    This experimental study investigated the back pressure (Pback) versus flow (U) relationship for 10 different tubes commonly used for semi-occluded vocal tract exercises, that is, eight straws of different lengths and diameters, a resonance tube, and a silicone tube similar to a Lax Vox tube. All tubes were assessed with the free end in air. The resonance tube and silicone tube were further assessed with the free end under water at the depths from 1 to 7 cm in steps of 1 cm. The results showed that relative changes in the diameter of straws affect Pback considerably more compared with the same amount of relative change in length. Additionally, once tubes are submerged into water, Pback needs to overcome the pressure generated by the water depth before flow can start. Under this condition, only a small increase in Pback was observed as the flow was increased. Therefore, the wider tubes submerged into water produced an almost constant Pback determined by the water depth, whereas the thinner straws in air produced relatively large changes to Pback as flow was changed. These differences may be taken advantage of when customizing exercises for different users and diagnoses and optimizing the therapy outcome.

  • 23. Aneman, A.
    et al.
    Svensson, M.
    Broome, M.
    Karolinska Institutet.
    Biber, B.
    Petterson, A.
    Fandriks, L.
    Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs2000Other (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

  • 24.
    Asem, Heba
    et al.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM. Karolinska Inst, Sweden.
    Abd El-Fattah, Ahmed
    Nafee, Noha
    Zhao, Ying
    Khalil, Labiba
    Muhammed, Mamoun
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.
    Hassan, Moustapha
    Kandil, Sherif
    Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer2016In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 13, p. 48-57Article in journal (Refereed)
    Abstract [en]

    Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods: AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1 nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results: The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions: The AlPc-based copolymer nanoparticles developed offer potential as a single agent multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.

  • 25.
    Ashokkumar, Manickam
    et al.
    Natl Inst Res TB, Dept HIV AIDS, Madras, Tamil Nadu, India.;Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Aralaguppe, Shambhu G.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Tripathy, Srikanth P.
    Natl Inst Res TB, Dept HIV AIDS, Madras, Tamil Nadu, India..
    Hanna, Luke Elizabeth
    Natl Inst Res TB, Dept HIV AIDS, Madras, Tamil Nadu, India..
    Neogi, Ujjwal
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses2018In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, no 9, article id e00063-18Article in journal (Refereed)
    Abstract [en]

    Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-Nef Delta gp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection. IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist. One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus. Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet. An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV. Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.

  • 26.
    Atefi, Seyed Reza
    et al.
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Electrical Bioimpedance cerebral monitoring. Preliminary results from measurements on stroke patients2012In: Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE, IEEE , 2012, p. 126-129Conference paper (Refereed)
    Abstract [en]

    Electrical Bioimpedance Spectroscopy (EBIS) is currently used in different tissue characterization applications. In this work we aim to use EBIS to study changes in electrical properties of the cerebral tissues after an incident of hemorrhage/ischemic stroke. To do so a case-control study was conducted using six controls and three stroke cases. The preliminary results of this study show that by using Cole-based analysis on EBIS measurements and analyzing the Cole parameters R0 and R∞, it is possible to detect changes on electrical properties of cerebral tissue after stroke. 

  • 27.
    Ayoglu, Burcu
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Kockum, Ingrid
    Olsson, Tomas
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 10-10Article in journal (Other academic)
  • 28. Bak, Z
    et al.
    Abildgård, L
    Lisander, B
    Janerot-Sjöberg, B
    Hälsouniversitetet, Linköping University.
    Transesophageal echocardiographic hemodynamic monitoring during preoperative acute normovolemic hemodilution.2000In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 92, no 5, p. 1250-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preoperative acute normovolemic hemodilution may compromise oxygen transport. The aims of our study were to describe the hemodynamic effects of normovolemic hemodilution and to determine its effect on systolic and diastolic cardiac function by multiplane transesophageal echocardiography.

    METHODS: In eight anesthetized patients (aged 13-51 yr) without heart disease, hemoglobin was reduced in steps from 123 +/- 8 (mean +/- SD) to 98 +/- 3 and to 79 +/- 5 g/l. Hemodynamic measurements (intravascular pressures, thermodilution cardiac output, and echocardiographic recordings) were obtained during a stabilization period and at each level of hemodilution. Left ventricular wall motion was monitored continuously, and Doppler variables, annular motion, and changes in ejection fractional area were analyzed off-line.

    RESULTS: During hemodilution, cardiac output by thermodilution increased by 16 +/- 7% and 26 +/- 10%, corresponding well to the increase in cardiac output as measured by Doppler (difference, 0.32 +/- 1.2 l/min). Systemic vascular resistance fell 16 +/- 14% and 23 +/- 9% and pulmonary capillary wedge pressure increased slightly (2 +/- 2 mmHg), whereas other pressures, heart rate, wall motion, and diastolic Doppler variables remained unchanged. Ejection fractional area change increased from 44 +/- 7% to 54 +/- 10% and 60 +/- 9% as a result of reduced end-systolic and increased end-diastolic left ventricular areas.

    CONCLUSIONS: A reduction in hemoglobin to 80 g/l during acute normovolemic hemodilution does not normally compromise systolic or diastolic myocardial function as determined by transesophageal echocardiography. Preload, left ventricular ejection fraction, and cardiac output increase with a concomitant fall in systemic vascular resistance.

  • 29. Bak, Z
    et al.
    Sjöberg, F
    Eriksson, O
    Steinvall, I
    Janerot-Sjöberg, Birgitta
    Department of Clinical Physiology, Heart Centre, Linköping University Hospital, Sweden.
    Cardiac dysfunction after burns2008In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 34, no 5, p. 603-609Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.

    PATIENTS AND METHODS: Ten consecutive adults (aged 36-89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36h after the burn.

    RESULTS: Half (n=5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36h after the burn (p< or =0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.

    CONCLUSION: Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.

  • 30. Bak, Z
    et al.
    Sjöberg, F
    Rousseau, A
    Steinvall, I
    Janerot-Sjöberg, Birgitta
    Department of Clinical Physiology, Heart Center, Linköping University Hospital.
    Human cardiovascular dose-response to supplemental oxygen2007In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, no 1, p. 15-24Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree.

    METHODS: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol.

    RESULTS: Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P < 0.05), and showed a linear, negative dose-response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change.

    CONCLUSION: There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

  • 31. Bak, Zoltan
    et al.
    Sjöberg, Folke
    Hälsouniversitetet, Linköping University.
    Eriksson, Olle
    Steinvall, Ingrid
    Janerot-Sjoberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Hemodynamic changes during resuscitation after burns using the Parkland formula2009In: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 66, no 2, p. 329-336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly.

    METHODS: Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body surface area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints.

    RESULTS: Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung water: intrathoracal blood volume ratio was increased 12 hours after the burn.

    CONCLUSIONS: Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.

  • 32.
    Ban, Yifang
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Geodesy and Geoinformatics.
    Fredman, David
    Jonsson, Martin
    Svensson, Leif
    Multi-Criteria Evaluations for Improved Placement of Defibrillators: Preliminary Results2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22, p. 78-Article in journal (Other academic)
  • 33. Baptista La, Filipa Martins
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH, Music Acoustics.
    Pregnancy and the Singing Voice: Reports From a Case Study2012In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 26, no 4, p. 431-439Article in journal (Refereed)
    Abstract [en]

    Objectives. Significant changes in body tissues occur during pregnancy; however, literature concerning the effects of pregnancy on the voice is sparse, especially concerning the professional classically trained voice. Hypotheses. Hormonal variations and associated bodily changes during pregnancy affect phonatory conditions, such as vocal fold motility and glottal adduction. Design. Longitudinal case study with a semiprofessional classically trained singer. Methods. Audio, electrolaryngograph, oral pressure, and air flow signals were recorded once a week during the last 12 weeks of pregnancy, 48 hours after birth and during the following consecutive 11 weeks. Vocal tasks included diminuendo sequences of the syllable /pae/sung at various pitches, and performing a Lied. Phonation threshold pressures (PTPs) and collision threshold pressures (CTPs), normalized amplitude quotient (NAQ), alpha ratio, and the dominance of the voice source fundamental were determined. Concentrations of sex female steroid hormones were measured on three occasions. A listening test of timbral brightness and vocal fatigue was carried out. Results. Results demonstrated significantly elevated concentrations of estrogen and progesterone during pregnancy, which were considerably reduced after birth. During pregnancy, CTPs and PTPs were high; and NAQ, alpha ratio, and dominance of the voice source fundamental suggested elevated glottal adduction. In addition, a perceptible decrease of vocal brightness was noted. Conclusions. The elevated CTPs and PTPs during pregnancy suggest reduced vocal fold motility and increased glottal adduction. These changes are compatible with expected effects of elevated concentrations of estrogen and progesterone on tissue viscosity and water retention.

  • 34. Bartonek, A.
    et al.
    Lidbeck, C. M.
    Gutierrez-Farewik, Elena
    KTH, School of Engineering Sciences (SCI), Mechanics, Biomechanics.
    Influence of external visual focus on gait in children with bilateral cerebral palsy2016In: Pediatric Physical Therapy, ISSN 0898-5669, E-ISSN 1538-005X, Vol. 28, no 4, p. 393-399Article in journal (Refereed)
    Abstract [en]

    Purpose: To explore whether focusing a target influenced gait in children with cerebral palsy (CP) and typical development (TD). Methods: Thirty children with bilateral CP (Gross Motor Function Classification System [GMFCS] I-III) and 22 with TD looked at a light at walkway end (Gaze Target) while walking and returned (No Target). Results: During Gaze versus No Target, children with TD reduced temporal-spatial parameters and movements in the sagittal (SPM) and transverse planes. In comparison, during Gaze Target, children in CP1 (GMFCS I) had larger trunk SPM, children in CP2 (GMFCS II) larger neck (SPM), and children in CP3 (GMFCS III) greater head and neck frontal plane movements, and reduced cadence and single support. Conclusions: Focusing a target altered gait in children with CP. Children in CP1 reduced movements similar to children with TD, children in CP2 behaved nearly unchanged, whereas children in CP3 reduced movements and temporalspatial parameters, potentially as a consequence of lack of sensory information from lower limbs.

  • 35. Baskaran, Karthikeyan
    et al.
    Rosén, Robert
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lewis, Peter
    Unsbo, Peter
    Gustafsson, Jörgen
    Benefit of Adaptive Optics Aberration Correction at Preferred Retinal Locus2012In: Optometry and Vision Science, ISSN 1040-5488, E-ISSN 1538-9235, Vol. 89, no 9Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of eccentric refractive correction and full aberration correction on both high and low contrast grating resolution at the preferred retinal locus (PRL) of a single low vision subject with a longstanding central scotoma.

    Methods: The subject was a 68 year-old female with bilateral absolute central scotoma due to Stargardt’s disease. She has developed a single PRL located 25° nasally of the damaged macula in her left eye, this being the better of the two eyes. High- (100%) and low contrast (25% & 10%) grating resolution acuity was evaluated using four different correction conditions. The first two corrections were solely refractive error corrections; namely habitual spectacle correction and full sphero-cylindrical correction. The latter two corrections were two versions of adaptive optics corrections of all aberrations; namely full sphero-cylindrical refractive correction with additional aberration correction and habitual spectacle correction with aberration correction.

    Results: The mean high contrast (100%) resolution acuity with her habitual correction was 1.06 logMAR, which improved to 1.00 logMAR with full sphero-cylindrical correction. Under the same conditions, low contrast (25%) acuity improved from 1.30 logMAR to 1.14 logMAR. With adaptive optics aberration correction, the high contrast resolution acuities improved to 0.92/0.89 logMAR and the low contrast acuities, to 1.06/1.04 logMAR under both correction modalities. The low contrast (10%) resolution acuity was 1.34 logMAR with adaptive optics aberration correction; however, with purely refractive error corrections she was unable to identify the orientation of the gratings.

    Conclusion: Correction of all aberrations using adaptive optics improves both high and low contrast resolution acuity at the PRL of a single low vision subject with longstanding absolute central scotoma.

  • 36. Baskaran, Karthikeyan
    et al.
    Unsbo, Peter
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Gustafsson, Jörgen
    Influence of Age on Peripheral Ocular Aberrations2011In: Optometry and Vision Science, ISSN 1040-5488, E-ISSN 1538-9235, Vol. 88, no 9, p. 1088-1098Article in journal (Refereed)
    Abstract [en]

    Purpose. To compare peripheral lower and higher order aberrations across the horizontal (+/- 40 degrees) and inferior (-20 degrees) visual fields in healthy groups of young and old emmetropes. Methods. We have measured off-axis aberrations in the groups of 30 younger (24 +/- 3 years) and 30 older (58 +/- 5 years) emmetropes. The aberrations of OD were measured using the COAS-HD VR Shack-Hartmann aberrometer in 10 degrees steps to +/- 40 degrees horizontally and -20 degrees inferiorly in the visual field. The aberrations were quantified with Zernike polynomials for a 4 mm pupil diameter. The second-order aberration coefficients were converted to their respective refraction components (M, J(45), and J(180)). Mixed between-within subjects, analysis of variance were used to determine whether there were significant differences in the refraction and aberration components for the between-subjects variable age and the within-subjects variable eccentricity. Results. Peripheral refraction components were similar in both age groups. Among the higher order coefficients, horizontal coma (C(3)(1)) and spherical aberration (C(4)(0)) varied mostly between the groups. Coma increased linearly with eccentricity, at a more rapid rate in the older group than in the younger group. Spherical aberration was more positive in the older group compared with the younger group. Higher order root mean square increased more rapidly with eccentricity in the older group. Conclusions. Like the axial higher order aberrations, the peripheral higher order aberrations of emmetropes increase with age, particularly coma and spherical aberration.

  • 37.
    Batool, Nazre
    KTH, School of Technology and Health (STH).
    Detection and Spatial Analysis of Hepatic Steatosis in Histopathology Images using Sparse Linear Models2016In: 2016 SIXTH INTERNATIONAL CONFERENCE ON IMAGE PROCESSING THEORY, TOOLS AND APPLICATIONS (IPTA), IEEE, 2016Conference paper (Refereed)
    Abstract [en]

    Hepatic steatosis is a defining feature of nonalcoholic fatty liver disease, emerging with the increasing incidence of obesity and metabolic syndrome. The research in image-based analysis of hepatic steatosis mostly focuses on the quantification of fat in biopsy images. This work furthers the image-based analysis of hepatic steatosis by exploring the spatial characteristics of fat globules in whole slide biopsy images after performing fat detection. An algorithm based on morphological filtering and sparse linear models is presented for fat detection. Then the spatial properties of detected fat globules in relation to the hepatic anatomical structures of central veins and portal tracts are explored. The test dataset consists of 38 high resolution images from 21 patients. The experimental results provide an insight into the size distributions of fat globules and their location with respect to the anatomical structures.

  • 38.
    Baxter, Brent S.
    et al.
    University of Utah.
    Hitchner, Lewis E.
    University of Utah.
    Maguire Jr., Gerald Q.
    Columbia University.
    A standard format for digital image exchange1982Book (Other academic)
  • 39.
    Baxter, Brent S.
    et al.
    University of Utah.
    Zeleznik, Michael P.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    What Types of Standards would be useful in PACS Activities1983In: Proceedings of the Society of Photo-Optical Instrumentation Engineers, ISSN 0361-0748, Vol. 418, p. 146-150Article in journal (Refereed)
  • 40.
    Benfeitas, Rui
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nielsen, Jens
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, A.
    New challenges to study heterogeneity in cancer redox metabolism2017In: Frontiers in Cell and Developmental Biology, ISSN 2296-634X, Vol. 5, no JUL, article id 65Article in journal (Refereed)
    Abstract [en]

    Reactive oxygen species (ROS) are important pathophysiological molecules involved in vital cellular processes. They are extremely harmful at high concentrations because they promote the generation of radicals and the oxidation of lipids, proteins, and nucleic acids, which can result in apoptosis. An imbalance of ROS and a disturbance of redox homeostasis are now recognized as a hallmark of complex diseases. Considering that ROS levels are significantly increased in cancer cells due to mitochondrial dysfunction, ROS metabolism has been targeted for the development of efficient treatment strategies, and antioxidants are used as potential chemotherapeutic drugs. However, initial ROS-focused clinical trials in which antioxidants were supplemented to patients provided inconsistent results, i.e., improved treatment or increased malignancy. These different outcomes may result from the highly heterogeneous redox responses of tumors in different patients. Hence, population-based treatment strategies are unsuitable and patient-tailored therapeutic approaches are required for the effective treatment of patients. Moreover, due to the crosstalk between ROS, reducing equivalents [e.g., NAD(P)H] and central metabolism, which is heterogeneous in cancer, finding the best therapeutic target requires the consideration of system-wide approaches that are capable of capturing the complex alterations observed in all of the associated pathways. Systems biology and engineering approaches may be employed to overcome these challenges, together with tools developed in personalized medicine. However, ROS- and redox-based therapies have yet to be addressed by these methodologies in the context of disease treatment. Here, we review the role of ROS and their coupled redox partners in tumorigenesis. Specifically, we highlight some of the challenges in understanding the role of hydrogen peroxide (H2O2), one of the most important ROS in pathophysiology in the progression of cancer. We also discuss its interplay with antioxidant defenses, such as the coupled peroxiredoxin/thioredoxin and glutathione/glutathione peroxidase systems, and its reducing equivalent metabolism. Finally, we highlight the need for system-level and patient-tailored approaches to clarify the roles of these systems and identify therapeutic targets through the use of the tools developed in personalized medicine. © 2017 Benfeitas, Uhlen, Nielsen and Mardinoglu.

  • 41.
    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.

  • 42.
    Bergenstråhle, Malin
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Thormann, Esben
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface Chemistry.
    Nordgren, Niklas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface Chemistry.
    Berglund, Lars
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Force Pulling of Single Cellulose Chains at the Crystalline Cellulose-Liquid Interface: A Molecular Dynamics Study2009In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 25, no 8, p. 4635-4642Article in journal (Refereed)
    Abstract [en]

    Pulling single cellulose molecules from a crystalline cellulose surface has been modeled by molecular dynamics (MD) simulations of the experimental procedure used in atomic force microscopy (AFM). Specifically, the aim of the study was to investigate cellulose interactions at desorption. Simulations were performed in both water and the organic solvent cyclohexane. Moreover, the effects of initial octamer conformation and orientation with respect to the surface chains were studied. A strong effect from the solvent was observed. In cyclohexane, normal forces of 200-500 pN and energies of 43.5 +/- 6.0 kJ/mol glucose unit were required to pull off the octamer. The normal forces in water were substantially lower, around 58 pN, and the energies were 18.2 +/- 3.6 kJ/mol glucose unit. In addition, the lateral components of the pull-off force were shown to provide information on initial conformation and orientation. Hydrogen bonds between the octamer and surface were analyzed and found to be an important factor in the pull-off behavior. Altogether, it was shown that MD provides detailed information on the desorption processes that may be useful for the interpretation of AFM experiments.

  • 43.
    Berggren, Karl
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Cascaded systems analysis of shift-variant image quality in slit-scanning breast tomosynthesis2018In: Medical PhysicsArticle in journal (Refereed)
  • 44.
    Berggren, Karl
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Spectral image quality and applications in breast tomosynthesis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the 1970s, it was determined that screening mammography is an efficient tool in fighting the increasing number of women dying from breast cancer, and many countries have established screening programs since then. Mammography systems have improved substantially over the years with one of the major advances being the transition from x-ray film to digital x-ray detectors. Following this development, the number of women dying from breast cancer has decreased, but there is still much room for improvement. One technology that is changing the breast imaging landscape is breast tomosynthesis; tomographic imaging with in-plane resolution similar to that of mammography, albeit limited height resolution. Breast tomosynthesis is commonly implemented with flat-panel detectors, but line detectors in a slit-scanning geometry can also be used. The latter configuration allows for more complex detector technologies, such as spectral photon-counting detectors that enable single-shot spectral imaging. The combination of spectral imaging and tomosynthesis opens up for a range of new applications, but the slit scanning geometry, which differs substantially from that of flat-panel tomosynthesis systems, and the factors affecting image quality have not been well understood. This thesis aims at filling this gap. Image quality and the parameters that influence image quality in spectral photon-counting slit-scanning breast tomosynthesis are characterized and analyzed using cascaded-systems modelling and linear image quality metrics. In addition, the thesis goes into characterizing the x-ray properties of breast tissue, an important input parameter for accurate material decomposition of in-vivo tissue. Material decomposition with spectral imaging opens up a range of applications, such as accurate measurement of volumetric breast density and spectral lesion characterization for decision support as part of mammography screening, and contrast-enhanced K-edge imaging for diagnostics. Tomosynthesis combined with material decomposition has the potential to improve these methods further by, for instance, separating lesions or regions of interest from surrounding fibro-glandular tissue in quantitative 3D maps of breast tissue.

  • 45.
    Berggren, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Philips Mammorgaphy Solutions.
    Cederström, Björn
    Philips Mammography Solutions.
    Lundqvist, Mats
    Philips Mammography Solutions.
    Fredenberg, Erik
    Philips Research.
    Characterization of photon-counting multislit breast tomosynthesis2018In: Medical Physics, E-ISSN 2473-4209Article in journal (Refereed)
    Abstract [en]

    Purpose: It has been shown that breast tomosynthesis may improve sensitivity and specificity compared to two-dimensional mammography, resulting in increased detection-rate of cancers or lowered call-back rates. The purpose of this study is to characterize a spectral photon-counting multislit breast tomosynthesis system that is able to do single-scan spectral imaging with multiple collimated x-ray beams. The system differs in many aspects compared to conventional tomosynthesis using energyintegrating flat-panel detectors. Methods: The investigated system was a prototype consisting of a dual-threshold photon-counting detector with 21 collimated line detectors scanning across the compressed breast. A review of the system is done in terms of detector, acquisition geometry, and reconstruction methods. Three reconstruction methods were used, simple back-projection, filtered back-projection and an iterative algebraic reconstruction technique. The image quality was evaluated by measuring the modulation transfer-function (MTF), normalized noise-power spectrum, detective quantum-efficiency (DQE), and artifact spread-function (ASF) on reconstructed spectral tomosynthesis images for a total-energy bin (defined by a low-energy threshold calibrated to remove electronic noise) and for a high-energy bin (with a threshold calibrated to split the spectrum in roughly equal parts). Acquisition was performed using a 29 kVp W/Al x-ray spectrum at a 0.24 mGy exposure. Results: The difference in MTF between the two energy bins was negligible, that is, there was no energy dependence on resolution. The MTF dropped to 50% at 1.5 lp/mm to 2.3 lp/mm in the scan direction and 2.4 lp/mm to 3.3 lp/mm in the slit direction, depending on the reconstruction method. The full width at half maximum of the ASF was found to range from 13.8 mm to 18.0 mm for the different reconstruction methods. The zero-frequency DQE of the system was found to be 0.72. The fraction of counts in the high-energy bin was measured to be 59% of the total detected spectrum. Scantimes ranged from 4 s to 16.5 s depending on voltage and current settings. Conclusions: The characterized system generates spectral tomosynthesis images with a dual-energy photon-counting detector. Measurements show a high DQE, enabling high image quality at a low dose, which is beneficial for low-dose applications such as screening. The single-scan spectral images open up for applications such as quantitative material decomposition and contrast-enhanced tomosynthesis. 

  • 46.
    Berggren, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Philips Mammography Solutions.
    Cederström, Björn
    Philips Mammography Solutions.
    Lundqvist, Mats
    Philips.
    Fredenberg, Erik
    Philips Research.
    Technical Note: Comparison of first‐ and second‐generation photon‐counting slit‐scanning tomosynthesis systems2018In: Medical PhysicsArticle in journal (Refereed)
    Abstract [en]

    Purpose: Digital breast tomosynthesis (DBT) is an emerging tool for breast-cancer screening and diagnostics. The purpose of this study is to present a second-generation photon-counting slitscanning DBT system and compare it to the first-generation system in terms of geometry and image quality. The study presents the first image-quality measurements on the second-generation system. Method: The geometry of the new system is based on a combined rotational and linear motion, in contrast to a purely rotational scan motion in the first generation. In addition, the calibration routines have been updated. Image quality was measured in the center of the image field in terms of in-slice modulation transfer function (MTF), artifact spread function (ASF), and in-slice detective quantum efficiency (DQE). Images were acquired using a W/Al 29 kVp spectrum at 13 mAs with 2 mm Al additional filtration and reconstructed using simple back-projection. Result: The in-slice 50% MTF was improved in the chest-mammilla direction, going from 3.2 to 3.5 lp/mm, and the zero-frequency DQE increased from 0.71 to 0.77. The MTF and ASF were otherwise found to be on par for the two systems. The new system has reduced in-slice variation of the tomographic angle. Conclusions: The new geometry is less curved, which reduces in-slice tomographic-angle variation, and increases the maximum compression height, making the system accessible for a larger population. The improvements in MTF and DQE were attributed to the updated calibration procedures. We conclude that the second-generation system maintains the key features of the photon-counting system while maintaining or improving image quality and improving the maximum compression height. 

  • 47.
    Berggren, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Eriksson, Mikael
    Hall, Per
    Wallis, Matthew
    Fredenberg, Erik
    In-vivo measurement of the effective atomic number of breast skin using spectral mammography2018In: Article in journal (Refereed)
  • 48.
    Berggren, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Philips Healthcare, S-17141 Solna, Sweden.
    Lundqvist, Mats
    Cederstrom, Bjorn
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Fredenberg, Erik
    Physical characterization of photon-counting tomosynthesis2015Conference paper (Refereed)
    Abstract [en]

    Tomosynthesis is emerging as a next generation technology in mammography. Combined with photon-counting detectors with the ability for energy discrimination, a novel modality is enabled - spectral tomosynthesis. Further advantages of photon-counting detectors in the context of tomosynthesis include elimination of electronic noise, efficient scatter rejection (in some geometries) and no lag. Fourier-based linear-systems analysis is a well-established method for optimizing image quality in two-dimensional x-ray systems. The method has been successfully adapted to three-dimensional imaging, including tomosynthesis, but several areas need further investigation. This study focuses on two such areas: 1) Adaption of the methodology to photon-counting detectors, and 2) violation of the shift-invariance and stationarity assumptions in non-cylindrical geometries. We have developed a Fourier-based framework to study the image quality in a photon-counting tomosynthesis system, assuming locally linear, stationary, and shift-invariant system response. The framework includes a cascaded-systems model to propagate the modulation-transfer function (MTF) and noise-power spectrum (NPS) through the system. The model was validated by measurements of the MTF and NPS. High degrees of non-shift invariance and non-stationarity were observed, in particular for the depth resolution as the angle of incidence relative the reconstruction plane varied throughout the imaging volume. The largest effects on image quality in a given point in space were caused by interpolation from the inherent coordinate system of the x-rays to the coordinate system that was used for reconstruction. This study is part of our efforts to fully characterize the spectral tomosynthesis system, we intend to extend the model further to include the detective-quantum efficiency, observer modelling, and spectral effects.

  • 49.
    Berglund, Emelie
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Maaskola, Jonas
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Schultz, Niklas
    Friedrich, Stefanie
    Marklund, Maja
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Bergenstrahle, Joseph
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Tarish, Firas
    Tanoglidi, Anna
    Vickovic, Sanja
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Larsson, Ludvig
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Salmén, Fredrik
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ogris, Christoph
    Wallenborg, Karolina
    Lagergren, Jens
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST).
    Ståhl, Patrik
    Sonnhammer, Erik
    Helleday, Thomas
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 2419Article in journal (Refereed)
    Abstract [en]

    Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.

  • 50. Berglund, S.
    et al.
    Magalhaes, I.
    Gaballa, A.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics. Karolinska Institutet, Sweden.
    Advances in umbilical cord blood cell therapy: the present and the future2017In: Expert Opinion on Biological Therapy, ISSN 1471-2598, E-ISSN 1744-7682, Vol. 17, no 6, p. 691-699Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy. Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI. It also provides an overview regarding the progress in adoptive cellular therapy using UCB. Expert opinion: UCB has been established as an important source of stem cells for HSCT. Successful strategies to overcome the limitations of UCBT, such as the limited cell numbers and naivety of the cells, are being developed, including novel methods to perform in vitro expansion of progenitor cells, and to improve their homing to the bone marrow. Promising early clinical trials of adoptive therapies with UCB cells, including non-immunological cells, are currently performed for viral infections, malignant diseases and in regenerative medicine.

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