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  • 1.
    Abouzayed, Ayman
    et al.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Tano, Hanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Nagy, Abel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Rinne, Sara S.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Wadeea, Fadya
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Kumar, Sharmishtaa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Westerlund, Kristina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Tolmachev, Vladimir
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Centrum Oncotheranost, Tomsk 634050, Russia.;Uppsala Univ, Sci Life Lab, S-75105 Uppsala, Sweden..
    Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer2020In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 12, no 10, article id 977Article in journal (Refereed)
    Abstract [en]

    The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.

  • 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 (pre-2005), 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 (pre-2005), 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 (pre-2005), 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.
    Akan, Rabia
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundberg, Fabian
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Ohlin, Hanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Johansson, Ulf
    Lund Univ, MAX IV Lab, S-22100 Lund, Sweden..
    Li, Kenan
    SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA..
    Sakdinawat, Anne
    SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA..
    Vogt, Ulrich
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Metal-Assisted Chemical Etching and Electroless Deposition for Fabrication of Hard X-ray Pd/Si Zone Plates2020In: Micromachines, E-ISSN 2072-666X, Vol. 11, no 3, article id 301Article in journal (Refereed)
    Abstract [en]

    Zone plates are diffractive optics commonly used in X-ray microscopes. Here, we present a wet-chemical approach for fabricating high aspect ratio Pd/Si zone plate optics aimed at the hard X-ray regime. A Si zone plate mold is fabricated via metal-assisted chemical etching (MACE) and further metalized with Pd via electroless deposition (ELD). MACE results in vertical Si zones with high aspect ratios. The observed MACE rate with our zone plate design is 700 nm/min. The ELD metallization yields a Pd density of 10.7 g/cm3, a value slightly lower than the theoretical density of 12 g/cm3. Fabricated zone plates have a grid design, 1:1 line-to-space-ratio, 30 nm outermost zone width, and an aspect ratio of 30:1. At 9 keV X-ray energy, the zone plate device shows a first order diffraction efficiency of 1.9%, measured at the MAX IV NanoMAX beamline. With this work, the possibility is opened to fabricate X-ray zone plates with low-cost etching and metallization methods.

  • 6.
    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.

  • 7.
    Alagic, Zlatan
    et al.
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden.;Karolinska Inst, Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Alagic, Haris
    Karolinska Inst, Inst Mol Med & Surg MMK, Diagnost Radiol, Stockholm, Sweden..
    Bujila, Robert
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Srivastava, Subhash
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Jasim, Saif
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Lindqvist, Maria
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Wick, Marius C.
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden.;Karolinska Inst, Inst Mol Med & Surg MMK, Diagnost Radiol, Stockholm, Sweden..
    First experiences of a low-dose protocol for CT-guided musculoskeletal biopsies combining different radiation dose reduction techniques2020In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 61, no 1, p. 28-36Article in journal (Refereed)
    Abstract [en]

    Background The use of computed tomography (CT) for image guidance during biopsies is a powerful approach. The method is, however, often associated with a significant level of radiation exposure to the patient and operator. Purpose To investigate if a low-dose protocol for CT-guided musculoskeletal (MSK) biopsies, including a combination of different radiation dose (RD) techniques, is feasible in a clinical setting. Material and Methods Fifty-seven patients underwent CT-guided fine-needle aspiration cytology (FNAC) utilizing the low-dose protocol (group A). A similar number of patients underwent CT-guided FNAC using the reference protocol (group B). Between-group comparisons comprised radiation dose, success rate, image quality parameters, and workflow. Results In group A, the mean total dose-length product (DLP) was 41.2 +/- 2.9 mGy*cm, which was statistically significantly lower than of group B (257.4 +/- 22.0 mGy*cm), corresponding to a mean dose reduction of 84% (P<0.001). The mean CTDIvol for the control scans were 1.88 +/- 0.09 mGy and 13.16 +/- 0.40 mGy for groups A and B, respectively (P < 0.001). The success rate in group A was 91.2% and 87.9% in group B (P = 0.56). No negative effect on image-quality parameters, time of FNAC, and number of control scans were found. Conclusion We successfully developed a low-dose protocol for CT-guided MSK biopsies that maintains diagnostic accuracy and image quality at a fraction of the RD compared to the reference biopsy protocol at our clinic.

  • 8.
    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.

  • 9. 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)
  • 10.
    Altai, M.
    et al.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Liu, Hao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Orlova, A.
    Div Mol Imaging, Dept Med Chem, Uppsala, Sweden..
    Tolmachev, V.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Gräslund, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Improving of molecular design of a novel Affibody-fused HER2-recognising anticancer toxin using radionuclide-based techniques2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S178-S178Article in journal (Other academic)
  • 11. Altai, M.
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    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)
  • 12. Altai, M.
    et al.
    Strand, J.
    Rosik, Daniel
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Selvaraju, R.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    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)
  • 13. 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)
  • 14.
    Altai, M.
    et al.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    Westerlund, Kristina
    KTH, School of Biotechnology (BIO), Protein Technology.
    Konijnenberg, M.
    Erasmus MC, Dept Nucl Med & Radiol, Rotterdam, Netherlands..
    Mitran, B.
    Div Mol Imaging, Uppsala, Sweden..
    Oroujeni, M.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    de Jong, M.
    Erasmus MC, Dept Nucl Med & Radiol, Rotterdam, Netherlands..
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Orlova, A.
    Div Mol Imaging, Uppsala, Sweden..
    Tolmachev, V.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    Pretargeted radionuclide therapy of HER2-expressing SKOV-3 human xenografts using an Affibody molecule-based PNA-mediated pretargeting2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S142-S142Article in journal (Other academic)
  • 15. 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.

  • 16. 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.

  • 17. 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.

  • 18. 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.

  • 19.
    Amini, Mehdi
    et al.
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Mostafaei, Shayan
    the Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Poursamimi, Mohamad
    the Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
    Chatterjee, Saikat
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Mansouri, Zahra
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Ghorbani, Mehdi
    the Department of Biomedical Engineering and Medical Physics, Shahid Beheshti University of medical sciences, Tehran, Iran.
    Shiri, Isaac
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Zaidi, Habib
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland; Geneva University Neurocenter, Geneva University, CH-1205 Geneva, Switzerland; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University of Groningen; University Medical Center Groningen, 9700 RB Groningen, Netherlands; Department of Nuclear Medicine, University of Southern Denmark, DK-500, Odense, Denmark..
    Interpretable PET/CT Radiomic Based Prognosis Modeling of NSCLC Recurrent Following Complete Resection2022In: 2022 IEEE NSS/MIC RTSD - IEEE Nuclear Science Symposium, Medical Imaging Conference and Room Temperature Semiconductor Detector Conference, Institute of Electrical and Electronics Engineers (IEEE) , 2022Conference paper (Refereed)
    Abstract [en]

    This study aimed to develop an interpretable prognostic model with a nomogram for Non-Small Cell Lung Cancer (NSCLC) recurrence prediction following complete resection, using multi-modality PET/CT fusion radiomics and patients' clinical features. Retrospectively, 181 NSCLC patients who had undergone18F-FDG PET/CT scan were enrolled and split into training (2/3) and testing (1/3) partitions. Before image fusion, PET and CT images were registered, resized to equal isotropic voxel size, and clipped and normalized. Guided Filtering Fusion GFF algorithm was used for image fusion. Two hundred eighteen radiomic features were extracted from each PET, CT, and fused image, including morphological, first-order statistical, and texture features. Clinical features included age, sex, smoking status, weight, radiation, chemotherapy, pathological stage, etc. Feature selection and univariate and multivariate modeling were performed using the CoxBoost algorithm. Harrell's Concordance index (C-index) was used to evaluate the performance of the models, and compare C test was used to statistically compare the performance of the models (p-values < 0.05 were considered significant). Clinical, Clinical+PET, Clinical+CT, and Clinical+GFF resulted in c-indices (confidence interval) of 0.701 (0.589-0.812), 0.757 (0.647-0.867), 0.706 (0.607, 0.807), and 0.824 (0.751-0.896), respectively. Statistical comparison of the performance of different models with the Clinical model revealed that while PET and GFF features can significantly increase the performance (p-values 0.009 and 0.001, respectively), CT features did not significantly improve the performance of the Clinical model (p-value 0.279). Therefore, the nomogram was developed based on the Clinical+GFF model (with the best performance). Radiomic features extracted from PET and PET/CT fusion images can improve the recurrence prognosis in NSCLC patients compared to the conventional clinical factors alone.

  • 20.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI.
    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.

  • 21.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI.
    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.
    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)
  • 22.
    Andersson, Ken G.
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Varasteh, Z.
    Rosenstedt, M.
    Rosestedt, M.
    Malm, Magdalena
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
    Sandström, M.
    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)
  • 23. Andersson, Malin
    et al.
    Jägervall, Karl
    Eriksson, Per
    Persson, Anders
    Granerus, Göran
    Wang, Chunliang
    KTH, School of Technology and Health (STH). Linköping Univ, Sweden.
    Smedby, Örjan
    KTH, School of Technology and Health (STH). 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.

    Download full text (pdf)
    Andersson 2015 renal artery stenosis
  • 24. Andersson, Thord
    et al.
    Romu, Thobias
    Karlsson, Anette
    Norén, Bengt
    Forsgren, Mikael F
    Smedby, Örjan
    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.

  • 25.
    Andreassi, Maria Grazia
    et al.
    CNR Natl Res Council Inst Clin Physiol, I-56125 Pisa, Italy..
    Haddy, Nadia
    Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth, Radiat Epidemiol Team, INSERM U1018,Gustave Roussy, F-94805 Villejuif, France..
    Harms-Ringdahl, Mats
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden..
    Campolo, Jonica
    ASST Grande Osped Metropolitano Niguarda, CNR Natl Res Council Inst Clin Physiol, I-20162 Milan, Italy..
    Borghini, Andrea
    CNR Natl Res Council Inst Clin Physiol, I-56125 Pisa, Italy..
    Chevalier, Francois
    Univ Caen Normandy, UMR6252 CIMAP, CEA, CNRS,ENSICAEN, F-14000 Caen, France.;Adv Resource Ctr HADrontherapy Europe ARCHADE, F-14000 Caen, France..
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Fresneau, Brice
    Univ Paris Saclay, Dept Children & Adolescents Oncol, Gustave Roussy, F-94805 Villejuif, France.;Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth, Canc & Radiat Team, INSERM U1018,Gustave Roussy, F-94805 Villejuif, France..
    Bolle, Stephanie
    Univ Paris Saclay, Dept Radiat Therapy, Gustave Roussy, F-94805 Villejuif, France..
    Fuentes, Manuel
    Univ Salamanca, Dept Med, CSIC USAL, Canc Res Ctr IBMCC,IBSAL,CSIC, Campus Miguel de Unamuno S-N, Salamanca 37007, Spain.;Univ Salamanca, Canc Res Ctr IBMCC, Gen Serv Cytometry, Prote Unit,CSIC USAL,IBSAL,CSIC, Campus Miguel de Unamuno S-N, Salamanca 37007, Spain..
    Haghdoost, Siamak
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden.;Univ Caen Normandy, UMR6252 CIMAP, CEA, CNRS,ENSICAEN, F-14000 Caen, France.;Adv Resource Ctr HADrontherapy Europe ARCHADE, F-14000 Caen, France..
    A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology: Rationale and Research Protocol of the HARMONIC Project2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 9, p. 8416-, article id 8416Article in journal (Refereed)
    Abstract [en]

    The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.

  • 26.
    Arian, Fatemeh
    et al.
    Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
    Amini, Mehdi
    Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva 4, CH-1211, Switzerland.
    Mostafaei, Shayan
    Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Rezaei Kalantari, Kiara
    Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran; Cardio-Oncology Research Center, Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
    Haddadi Avval, Atlas
    School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
    Shahbazi, Zahra
    Department of Biostatistics, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.
    Kasani, Kianosh
    Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran.
    Bitarafan Rajabi, Ahmad
    Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran; Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran; Cardiovascular interventional research center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
    Chatterjee, Saikat
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Oveisi, Mehrdad
    Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Kings College London, London, UK; Department of Computer Science, University of British Columbia, Vancouver BC, Canada.
    Shiri, Isaac
    Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva 4, CH-1211, Switzerland.
    Zaidi, Habib
    Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva 4, CH-1211, Switzerland; Geneva University Neurocenter, Geneva University, Geneva, Switzerland; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Department of Nuclear Medicine, University of Southern Denmark, Odense, Denmark.
    Myocardial Function Prediction After Coronary Artery Bypass Grafting Using MRI Radiomic Features and Machine Learning Algorithms2022In: Journal of digital imaging, ISSN 0897-1889, E-ISSN 1618-727X, Vol. 35, no 6, p. 1708-1718Article in journal (Refereed)
    Abstract [en]

    The main aim of the present study was to predict myocardial function improvement in cardiac MR (LGE-CMR) images in patients after coronary artery bypass grafting (CABG) using radiomics and machine learning algorithms. Altogether, 43 patients who had visible scars on short-axis LGE-CMR images and were candidates for CABG surgery were selected and enrolled in this study. MR imaging was performed preoperatively using a 1.5-T MRI scanner. All images were segmented by two expert radiologists (in consensus). Prior to extraction of radiomics features, all MR images were resampled to an isotropic voxel size of 1.8 × 1.8 × 1.8 mm3. Subsequently, intensities were quantized to 64 discretized gray levels and a total of 93 features were extracted. The applied algorithms included a smoothly clipped absolute deviation (SCAD)–penalized support vector machine (SVM) and the recursive partitioning (RP) algorithm as a robust classifier for binary classification in this high-dimensional and non-sparse data. All models were validated with repeated fivefold cross-validation and 10,000 bootstrapping resamples. Ten and seven features were selected with SCAD-penalized SVM and RP algorithm, respectively, for CABG responder/non-responder classification. Considering univariate analysis, the GLSZM gray-level non-uniformity-normalized feature achieved the best performance (AUC: 0.62, 95% CI: 0.53–0.76) with SCAD-penalized SVM. Regarding multivariable modeling, SCAD-penalized SVM obtained an AUC of 0.784 (95% CI: 0.64–0.92), whereas the RP algorithm achieved an AUC of 0.654 (95% CI: 0.50–0.82). In conclusion, different radiomics texture features alone or combined in multivariate analysis using machine learning algorithms provide prognostic information regarding myocardial function in patients after CABG.

  • 27.
    Arsana, Komang G.Y.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Saladino, Giovanni
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Brodin, Bertha
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Toprak, Muhammet
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Laboratory Liquid-Jet X-ray Microscopy and X-ray Fluorescence Imaging for Biomedical Applications2024In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 2, article id 920Article in journal (Refereed)
    Abstract [en]

    Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, liquid-jet soft X-ray microscopy (SXM) can provide morphological information on living cells without staining. Furthermore, X-ray fluorescence imaging (XFI) permits the tracking of contrast agents in vivo with high elemental specificity, going beyond attenuation contrast. In this study, we established a methodology to investigate nanoparticle (NP) interactions in vitro and in vivo, solely based on X-ray imaging. We employed soft (0.5 keV) and hard (24 keV) X-rays for cellular studies and preclinical evaluations, respectively. Our results demonstrated the possibility of localizing NPs in the intracellular environment via SXM and evaluating their biodistribution with in vivo multiplexed XFI. We envisage that laboratory liquid-jet X-ray technology will significantly contribute to advancing our understanding of biological systems in the field of nanomedical research.

  • 28.
    Astaraki, Mehdi
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. Karolinska Univ Sjukhuset, Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden..
    Smedby, Örjan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Wang, Chunliang
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Prior-aware autoencoders for lung pathology segmentation2022In: Medical Image Analysis, ISSN 1361-8415, E-ISSN 1361-8423, Vol. 80, p. 102491-, article id 102491Article in journal (Refereed)
    Abstract [en]

    Segmentation of lung pathology in Computed Tomography (CT) images is of great importance for lung disease screening. However, the presence of different types of lung pathologies with a wide range of heterogeneities in size, shape, location, and texture, on one side, and their visual similarity with respect to surrounding tissues, on the other side, make it challenging to perform reliable automatic lesion seg-mentation. To leverage segmentation performance, we propose a deep learning framework comprising a Normal Appearance Autoencoder (NAA) model to learn the distribution of healthy lung regions and re-construct pathology-free images from the corresponding pathological inputs by replacing the pathological regions with the characteristics of healthy tissues. Detected regions that represent prior information re-garding the shape and location of pathologies are then integrated into a segmentation network to guide the attention of the model into more meaningful delineations. The proposed pipeline was tested on three types of lung pathologies, including pulmonary nodules, Non-Small Cell Lung Cancer (NSCLC), and Covid-19 lesion on five comprehensive datasets. The results show the superiority of the proposed prior model, which outperformed the baseline segmentation models in all the cases with significant margins. On av-erage, adding the prior model improved the Dice coefficient for the segmentation of lung nodules by 0.038, NSCLCs by 0.101, and Covid-19 lesions by 0.041. We conclude that the proposed NAA model pro-duces reliable prior knowledge regarding the lung pathologies, and integrating such knowledge into a prior segmentation network leads to more accurate delineations.

  • 29. Bakowski Holtryd, Mietek
    et al.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    X-ray sensor, method for constructing an x-ray sensor and an x-ray imaging system comprising such an x-ray sensor2020Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    An X-ray sensor (1) having an active detector region including a plurality of detector diodes (2) arranged on a surface region (3) of the X-ray sensor (1), a junction termination (4) surrounding the surface area (3) including the plurality of detector diodes (2), the junction termination (4) including a guard (5) arranged closest to the end of the surface region (3), a field stop (6) arranged outside the guard (2) and a number N of field limiting rings, FLRs (7) arranged between the guard (5) and the field stop (6), wherein each of the FLRs (7) are placed at positions selected so that distances between different FLRs (7) and between the guard and the first FLR lie within an effective area, the effective area being bounded by the lines α=(10+1.3×(n−1)) μm and β=(5+1.05×(n−1)) μm.

  • 30. Bakowski Holtryd, Mietek
    et al.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    X-ray sensor, x-ray detector system and x-ray imaging system2018Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Disclosed is an x-ray sensor having an active detector region including a plurality of detector diodes at a first side of the sensor, and with placement of the junction termination at a second opposite side of the sensor. Normally, this implies that the junction termination is moved from the top side where the active detector area is located to the bottom side of the sensor, allowing for full utilization of the active detector area at the top side with detector diodes to the very edge of the sensor.  

  • 31. Bakowski Holtryd, Mietek
    et al.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    X-ray sensor, x-ray detector system and x-ray imaging system2019Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    There is provided an x-ray sensor (21) comprising an active detector region including a plurality of detector diodes (22) at a first side of the sensor, and a common junction termination (23) at a second opposite side of the sensor. Normally, this implies that the junction termination (23) is moved from the top side where the active detector area is located to the bottom side of the sensor, allowing for full utilization of the active detector area at the top side with detector diodes to the very edge of the sensor.  

  • 32.
    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)
  • 33.
    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)
  • 34.
    Bendazzoli, Simone
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Brusini, Irene
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alfred Nobels Alle 23,D3, S-14152 Huddinge, Sweden..
    Damberg, Peter
    Karolinska Inst, Dept Clin Neurosci, Tomtebodavagen 18A P1 5, S-17177 Stockholm, Sweden..
    Smedby, Örjan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Andersson, Leif
    Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab Uppsala, Biomedicinskt Ctr BMC, Husargatan 3, S-75237 Uppsala, Sweden..
    Wang, Chunliang
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Automatic rat brain segmentation from MRI using statistical shape models and random forest2019In: MEDICAL IMAGING 2019: IMAGE PROCESSING / [ed] Angelini, ED Landman, BA, SPIE-INT SOC OPTICAL ENGINEERING , 2019, article id 1094920Conference paper (Refereed)
    Abstract [en]

    In MRI neuroimaging, the shimming procedure is used before image acquisition to correct for inhomogeneity of the static magnetic field within the brain. To correctly adjust the field, the brain's location and edges must first be identified from quickly-acquired low resolution data. This process is currently carried out manually by an operator, which can be time-consuming and not always accurate. In this work, we implement a quick and automatic technique for brain segmentation to be potentially used during the shimming. Our method is based on two main steps. First, a random forest classifier is used to get a preliminary segmentation from an input MRI image. Subsequently, a statistical shape model of the brain, which was previously generated from ground-truth segmentations, is fitted to the output of the classifier to obtain a model-based segmentation mask. In this way, a-priori knowledge on the brain's shape is included in the segmentation pipeline. The proposed methodology was tested on low resolution images of rat brains and further validated on rabbit brain images of higher resolution. Our results suggest that the present method is promising for the desired purpose in terms of time efficiency, segmentation accuracy and repeatability. Moreover, the use of shape modeling was shown to be particularly useful when handling low-resolution data, which could lead to erroneous classifications when using only machine learning-based methods.

  • 35.
    Bengtsson, Ivar
    et al.
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Optimization and Systems Theory. RaySearch Labs AB, Res, Stockholm, Sweden..
    Finnson, A.
    RaySearch Labs AB, Res, Stockholm, Sweden..
    Automated online adaptive dose restoration using cross-entropy objectives2023In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 182, p. S675-S676Article in journal (Other academic)
  • 36.
    Bengtsson, Ivar
    et al.
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Optimization and Systems Theory. RaySearch Labs AB, SE-10430 Stockholm, Sweden..
    Forsgren, Anders
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Optimization and Systems Theory.
    Fredriksson, Albin
    RaySearch Labs AB, SE-10430 Stockholm, Sweden..
    Implications of using the clinical target distribution as voxel-weights in radiation therapy optimization2023In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 68, no 9, article id 095005Article in journal (Refereed)
    Abstract [en]

    Objective. Delineating and planning with respect to regions suspected to contain microscopic tumor cells is an inherently uncertain task in radiotherapy. The recently proposed clinical target distribution (CTD) is an alternative to the conventional clinical target volume (CTV), with initial promise. Previously, using theCTDin planning has primarily been evaluated in comparison to a conventionally defined CTV. Wepropose to compare theCTDapproach against CTVmargins of various sizes, dependent on the threshold at which the tumor infiltration probability is considered relevant. Approach. First, a theoretical framework is presented, concerned with optimizing the trade-off between the probability of sufficient target coverage and the penalties associated with high dose. From this framework we derive conventional CTV-based planning and contrast it with theCTDapproach. The approaches are contextualized further by comparison with established methods for managing geometric uncertainties. Second, for both one- and three-dimensional phantoms, we compare a set of CTDplans created by varying the target objective function weight against a set of plans created by varying both the target weight and the CTVmargin size. Main results. The results show that CTD-based planning gives slightly inefficient trade-offs between the evaluation criteria for a case in which near-minimum target dose is the highest priority. However, in a case when sparing a proximal organ at risk is critical, theCTDis better at maintaining sufficiently high dose toward the center of the target. Significance. Weconclude that CTD-based planning is a computationally efficient method for planning with respect to delineation uncertainties, but that the inevitable effects on the dose distribution should not be disregarded.

  • 37.
    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.

  • 38.
    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.

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  • 39.
    Berggren, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Philips Mammography Solutions, 164 40 Kista, Sweden.
    Cederstrom, Bjorn
    Lundqvist, Mats
    Fredenberg, Erik
    Cascaded systems analysis of shift-variant image quality in slit-scanning breast tomosynthesis2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 10, p. 4392-4401Article in journal (Refereed)
  • 40.
    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. 

  • 41.
    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 physics (Lancaster), ISSN 0094-2405, Vol. 45, no 2, p. 635-638Article 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. 

  • 42.
    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)
  • 43.
    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.

  • 44.
    Bermo, Mohammed
    et al.
    Virginia Tech Carilion Sch Med, Roanoke, VA 24016 USA..
    Abdelgalil, Mohammed Saqr
    KTH, School of Electrical Engineering and Computer Science (EECS), Human Centered Technology, Media Technology and Interaction Design, MID. Univ Eastern Finland, Sch Comp, Joensuu Campus, Joensuu, Finland..
    Hoffman, Hunter
    Univ Washington, Seattle, WA 98195 USA..
    Patterson, David
    Univ Washington, Seattle, WA 98195 USA..
    Sharar, Sam
    Univ Washington, Seattle, WA 98195 USA..
    Minoshima, Satoshi
    Univ Utah, Salt Lake City, UT USA..
    Lewis, David H.
    Univ Washington, Seattle, WA 98195 USA..
    Utility of SPECT Functional Neuroimaging of Pain2021In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 12, article id 705242Article in journal (Refereed)
    Abstract [en]

    Functional neuroimaging modalities vary in spatial and temporal resolution. One major limitation of most functional neuroimaging modalities is that only neural activation taking place inside the scanner can be imaged. This limitation makes functional neuroimaging in many clinical scenarios extremely difficult or impossible. The most commonly used radiopharmaceutical in Single Photon Emission Tomography (SPECT) functional brain imaging is Technetium 99 m-labeled Ethyl Cysteinate Dimer (ECD). ECD is a lipophilic compound with unique pharmacodynamics. It crosses the blood brain barrier and has high first pass extraction by the neurons proportional to regional brain perfusion at the time of injection. It reaches peak activity in the brain 1 min after injection and is then slowly cleared from the brain following a biexponential mode. This allows for a practical imaging window of 1 or 2 h after injection. In other words, it freezes a snapshot of brain perfusion at the time of injection that is kept and can be imaged later. This unique feature allows for designing functional brain imaging studies that do not require the patient to be inside the scanner at the time of brain activation. Functional brain imaging during severe burn wound care is an example that has been extensively studied using this technique. Not only does SPECT allow for imaging of brain activity under extreme pain conditions in clinical settings, but it also allows for imaging of brain activity modulation in response to analgesic maneuvers whether pharmacologic or non-traditional such as using virtual reality analgesia. Together with its utility in extreme situations, SPECTS is also helpful in investigating brain activation under typical pain conditions such as experimental controlled pain and chronic pain syndromes.

  • 45.
    Bertilson, M.
    et al.
    Eclipse Optics, Vasagatan 52, Stockholm, Sweden, Vasagatan 52.
    von Hofsten, O.
    Eclipse Optics, Vasagatan 52, Stockholm, Sweden, Vasagatan 52.
    Maltz, J. S.
    GE HealthCare, Waukesha, WI, United States of America.
    Taphorn, K.
    Munich Institute of Biomedical Engineering, Technical University of Munich, D-85748, Garching, Germany; Chair of Biomedical Physics, Department of Physics, TUM School of Natural Sciences, Technical University of Munich, D-85748 Garching, Germany; Research Group Biomedical Imaging Physics, Department of Physics, TUM School of Natural Sciences, Technical University of Munich, D-85748 Garching, Germany.
    Herzen, J.
    Munich Institute of Biomedical Engineering, Technical University of Munich, D-85748, Garching, Germany; Chair of Biomedical Physics, Department of Physics, TUM School of Natural Sciences, Technical University of Munich, D-85748 Garching, Germany; Research Group Biomedical Imaging Physics, Department of Physics, TUM School of Natural Sciences, Technical University of Munich, D-85748 Garching, Germany.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Analyzer-free hard x-ray interferometry2024In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 69, no 4, article id 045011Article in journal (Refereed)
    Abstract [en]

    Objective. To enable practical interferometry-based phase contrast CT using standard incoherent x-ray sources, we propose an imaging system where the analyzer grating is replaced by a high-resolution detector. Since there is no need to perform multiple exposures (with the analyzer grating at different positions) at each scan angle, this scheme is compatible with continuous-rotation CT apparatus, and has the potential to reduce patient radiation dose and patient motion artifacts. Approach. Grating-based x-ray interferometry is a well-studied technique for imaging soft tissues and highly scattering objects embedded in such tissues. In addition to the traditional x-ray absorption-based image, this technique allows reconstruction of the object phase and small-angle scattering information. When using conventional incoherent, polychromatic, hard x-ray tubes as sources, three gratings are usually employed. To sufficiently resolve the pattern generated in these interferometers with contemporary x-ray detectors, an analyzer grating is used, and consequently multiple images need to be acquired for each view angle. This adds complexity to the imaging system, slows image acquisition and thus increases sensitivity to patient motion, and is not dose efficient. By simulating image formation based on wave propagation, and proposing a novel phase retrieval algorithm based on a virtual grating, we assess the potential of a analyzer-grating-free system to overcome these limitations. Main results. We demonstrate that the removal of the analyzer-grating can produce equal image contrast-to-noise ratio at reduced dose (by a factor of 5), without prolonging scan duration. Significance. By demonstrating that an analyzer-free CT system, in conjuction with an efficient phase retrieval algorithm, can overcome the prohibitive dose and workflow penalties associated grating-stepping, an alternative path towards realizing clinical inteferometric CT appears possible.

  • 46.
    Bilic, Patrick
    et al.
    Tech Univ Munich, Dept Informat, Munich, Germany..
    Li, Hongwei Bran
    Tech Univ Munich, Dept Informat, Munich, Germany.;Univ Zurich, Dept Quantitat Biomed, Zurich, Switzerland..
    Wang, Chunliang
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Menze, Bjoern
    Tech Univ Munich, Dept Informat, Munich, Germany.;Univ Zurich, Dept Quantitat Biomed, Zurich, Switzerland..
    The Liver Tumor Segmentation Benchmark (LiTS)2023In: Medical Image Analysis, ISSN 1361-8415, E-ISSN 1361-8423, Vol. 84, p. 102680-, article id 102680Article in journal (Refereed)
    Abstract [en]

    In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

  • 47.
    Birnbaum, Bernard A.
    et al.
    New York University.
    Noz, Marilyn E.
    New York University.
    Chapnick, Jeffrey V.
    New York University.
    Sanger, Joseph J.
    New York University.
    Megibow, Alec J.
    New York University.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Weinreb, Jeffrey C.
    New York University.
    Kaminer, Evan M.
    New York University.
    Kramer, Elissa L.
    New York University.
    Hepatic hemangiomas: diagnosis with fusion of MR, CT, and Tc-99m-labeled red blood cell SPECT images1991In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 181, no 2, p. 469-474Article in journal (Refereed)
    Abstract [en]

    A method of image analysis was developed for correlation of hemangiomas detected at computed tomography {(CT)} and/or magnetic resonance {(MR)} imaging with increased blood pool activity evident at single photon emission {CT} {(SPECT)} performed after labeling of red blood cells with technetium-99m. Image analysis was performed in 20 patients with 35 known hepatic hemangiomas. After section thickness and pixel sizes of the different studies were matched, intrinsic landmarks were chosen to identify anatomically corresponding locations. Regions of interest {(ROIs)} drawn on the {CT} and/or {MR} images were translated, rotated, and reprojected to match the areas of interest on the corresponding {SPECT} images by means of a two-dimensional polynomial-based warping algorithm. Analysis of {ROIs} on 30 {SPECT-MR} and 20 {SPECT-CT} pairs of registered images provided absolute confirmation that 34 suspected hemangiomas identified on {SPECT} images correlated exactly with lesions seen on {CT} and/or {MR} images. Accuracy of fusion was within an average of 1.5 pixels +/- 0.8 (+/- 1 standard deviation). The technique enabled diagnostic confirmation of hemangiomas as small as 1.0 cm and proved useful for evaluating lesions located adjacent to intrahepatic vessels.

  • 48.
    Birnbaum, Bernard A.
    et al.
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Chapnick, Jeffrey V
    New York University.
    Sanger, Joseph J.
    New York University.
    Megibow, Alec J.
    New York University.
    Maguire Jr., Gerald Q.
    Columbia University, Computer Science.
    Weinreb, Jeffrey C.
    New York University.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Clinical Evaluation of Image Fusion Using MR Imaging, CT, and SPECT-RBC Images of Hepatic Hemangiomas1990In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 177, p. P228-Article in journal (Refereed)
  • 49. Blystad, I
    et al.
    Håkansson, I
    Tisell, A
    Ernerudh, J
    Smedby, Örjan
    aFrom the Departments of Radiology and Medical and Health Sciences (I.B., Ö.S.) bCentre for Medical Image Science and Visualization (I.B., A.T., Ö.S., P.L., E.-M.L.)Linköping University.
    Lundberg, P
    Larsson, E-M
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 1, p. 94-100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions.

    MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis.

    RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained.

    CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

  • 50.
    Blystad, I
    et al.
    Linköping Univ, Dept Radiol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden..
    Warntjes, J. B. M.
    Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Div Cardiovasc Med, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Smedby, Örjan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. Linköping Univ, Dept Radiol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden..
    Lundberg, P.
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Dept Radiat Phys, Linköping, Sweden..
    Larsson, E-M
    Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Uppsala Univ, Dept Surg Sci, Radiol, Uppsala, Sweden..
    Tisell, A.
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Dept Radiat Phys, Linköping, Sweden..
    Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 17986Article in journal (Refereed)
    Abstract [en]

    Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R-1), transverse relaxation (R-2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R-1-difference-map. The quantitative R-1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

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