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  • 1. 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, Tidigare Institutioner, Teleinformatik.
    Reddy, David P.
    Comparison of three methods used for fusion of SPECT-CT images of liver matastases1998Inngår i: Fusion98, International Conference on Multisource-Mulltisensor Information Fusion / [ed] Hamid R. Arabnia and Dongping (Daniel) Zhu, CSREA Press , 1998, s. 435-442Konferansepaper (Fagfellevurdert)
    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.

  • 2. Aitken, Candice L.
    et al.
    Mahmoud, Faaiza
    McGuinness, Georgeann
    Kramer, Elissa L.
    Maguire, Gerald Q. Jr.
    KTH, Tidigare Institutioner, Mikroelektronik och informationsteknik, IMIT.
    Noz, Marilyn E.
    New York University.
    Tumor localization and image registration of F-18FDG coincidence detection scans with computed tomographic scans2002Inngår i: Clinical Nuclear Medicine, ISSN 0363-9762, E-ISSN 1536-0229, Vol. 27, nr 4, s. 275-282Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3.
    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, Tidigare Institutioner, Teleinformatik.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Tumor localization and image registration of 18-FDG SPECT scans with CT scans1999Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 40, nr 5, s. 290P-291PArtikkel i tidsskrift (Fagfellevurdert)
    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.
    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 motion2010Inngår i: Ultrasound, ISSN 1742-271X, Vol. 18, nr 3, s. 140-147Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5.
    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, Skolan för informations- och kommunikationsteknik (ICT), Mikroelektronik och Informationsteknik, 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 arthroplasty2005Inngår i: Medical Imaging 2005: Image Processing, Pt 1-3 / [ed] Fitzpatrick, JM; Reinhardt, JM, SPIE - The International Sooceity for Optical Engineeering , 2005, Vol. 5747, s. 1155-1164Konferansepaper (Fagfellevurdert)
    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.

  • 6. Altai, M.
    et al.
    Honarvar, H.
    Wallberg, H.
    Strand, J.
    Varasteh, Z.
    Orlova, A.
    Dunas, F.
    Sandstrom, M.
    Rosestedt, M.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tolmachev, V.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with Re-1882013Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, s. S219-S220Artikkel i tidsskrift (Annet vitenskapelig)
  • 7. Altai, M.
    et al.
    Perols, Anna
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi (stängd 20130101).
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi (stängd 20130101).
    Sandström, M.
    Boschetti, F.
    Orlova, A.
    Tolmachev, V.
    Evaluation of a maleimido derivative of NODAGA for site-specific In-111-labeling of Affibody molecules2011Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 38, s. S146-S146Artikkel i tidsskrift (Annet vitenskapelig)
  • 8. Altai, M.
    et al.
    Strand, J.
    Rosik, Daniel
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi (stängd 20130101).
    Selvaraju, R.
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi (stängd 20130101).
    Orlova, A.
    Tolmachev, V.
    Comparative evaluation of anti-HER2 affibody molecules labeled with 68Ga and 111In using maleimido derivatives of DOTA and NODAGA.2012Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, s. S299-S299Artikkel i tidsskrift (Fagfellevurdert)
  • 9. Altai, M.
    et al.
    Wallberg, H.
    Honarvar, H.
    Strand, J.
    Orlova, A.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Varasteh, Z.
    Sandström, M.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tolmachev, V.
    Re-188-Z(HER2: V2), a promising targeting agent against HER2-expressing tumors: in vitro and in vivo assessment2013Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, s. S119-S119Artikkel i tidsskrift (Annet vitenskapelig)
  • 10. Altai, M.
    et al.
    Westerlund, Kristina
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Velletta, J.
    Mitran, B.
    Honarvar, H.
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and 177Lu labeling2017Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 54, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 11. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    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 NODAGA2012Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, nr 4, s. 518-529Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 12. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tsourma, Maria
    Mitran, Bogdan
    Honarvar, Hadis
    Robillard, Marc
    Rossin, Raffaella
    ten Hoeve, Wolter
    Lubberink, Mark
    Orlova, Anna
    Karlström, Amelie Eriksson
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tolmachev, Vladimir
    Feasibility of Affibody-Based Bioorthogonal Chemistry Mediated Radionuclide Pretargeting2016Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, nr 3, s. 431-436Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 13. Altai, Mohamed
    et al.
    Wållberg, Helena
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Honarvar, Hadis
    Strand, Joanna
    Orlova, Anna
    Varasteh, Zohreh
    Sandström, Mattias
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Larsson, Erik
    Strand, Sven-Erik
    Lubberink, Mark
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. Uppsala University, Sweden.
    Tolmachev, Vladimir
    Re-188-Z(HER2:V2), a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment2014Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, nr 11, s. 1842-1848Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 14.
    Anderlind, Eva
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Människa-datorinteraktion, MDI (stängd 20111231).
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Lind, Bengt K.
    Karolinska Institute, Department of Medical Radiation Physics.
    Maguire, Gerald Q. Jr.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Will haptic feedback speed up medical imaging? An application to radiation treatment planning2008Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, nr 1, s. 32-37Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 15.
    Anderlind, Eva
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Människa-datorinteraktion, MDI (stängd 20111231).
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, Skolan för datavetenskap och kommunikation (CSC), Människa-datorinteraktion, MDI (stängd 20111231).
    Maguire Jr., Gerald Q.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Lind, Bengt K.
    Karolinska Institute, Medical Radiation Physics.
    The value of haptic feedback in medical imaging and treatment planning2006Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 81, s. 1277-Artikkel i tidsskrift (Fagfellevurdert)
  • 16.
    Andersson, Ken G.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Varasteh, Z.
    Rosenstedt, M.
    Rosestedt, M.
    Malm, M.
    KTH.
    Sandström, M.
    KTH.
    Tolmachev, V.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Orlova, A.
    111In-labeled NOTA-conjugated Affibody molecules for visualization of HER3 expression in malignant tumors2014Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, s. S311-S311Artikkel i tidsskrift (Annet vitenskapelig)
  • 17. Andersson, Malin
    et al.
    Jägervall, Karl
    Eriksson, Per
    Persson, Anders
    Granerus, Göran
    Wang, Chunliang
    Linköping Univ, Sweden.
    Smedby, Örjan
    Linköping Univ, Sweden.
    How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance2015Inngår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 15, artikkel-id 42Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 18. Andersson, Thord
    et al.
    Romu, Thobias
    Karlsson, Anette
    Norén, Bengt
    Forsgren, Mikael F
    Smedby, Örjan
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Medicinsk bildbehandling och visualisering. Linköping University.
    Kechagias, Stergios
    Almer, Sven
    Lundberg, Peter
    Borga, Magnus
    Leinhard, Olof Dahlqvist
    Consistent intensity inhomogeneity correction in water-fat MRI2015Inngår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 19.
    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 exchange1982Bok (Annet vitenskapelig)
  • 20.
    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 Activities1983Inngår i: Proceedings of the Society of Photo-Optical Instrumentation Engineers, ISSN 0361-0748, Vol. 418, s. 146-150Artikkel i tidsskrift (Fagfellevurdert)
  • 21.
    Bennati, Paolo
    et al.
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik.
    Dasu, A.
    Colarieti-Tosti, Massimiliano
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Medicinsk bildteknik.
    Lönn, Gustaf
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik.
    Larsson, David
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Medicinsk bildteknik.
    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 radiotherapy2017Inngår i: Journal of Instrumentation, ISSN 1748-0221, E-ISSN 1748-0221, Vol. 12, nr 5, artikkel-id C05009Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 22.
    Berggren, Karl
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Cascaded systems analysis of shift-variant image quality in slit-scanning breast tomosynthesis2018Inngår i: Medical PhysicsArtikkel i tidsskrift (Fagfellevurdert)
  • 23.
    Berggren, Karl
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Spectral image quality and applications in breast tomosynthesis2018Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • 24.
    Berggren, Karl
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik. Philips Mammorgaphy Solutions.
    Cederström, Björn
    Philips Mammography Solutions.
    Lundqvist, Mats
    Philips Mammography Solutions.
    Fredenberg, Erik
    Philips Research.
    Characterization of photon-counting multislit breast tomosynthesis2018Inngår i: Medical Physics, E-ISSN 2473-4209Artikkel i tidsskrift (Fagfellevurdert)
    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. 

  • 25.
    Berggren, Karl
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik. 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 systems2018Inngår i: Medical PhysicsArtikkel i tidsskrift (Fagfellevurdert)
    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. 

  • 26.
    Berggren, Karl
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Eriksson, Mikael
    Hall, Per
    Wallis, Matthew
    Fredenberg, Erik
    In-vivo measurement of the effective atomic number of breast skin using spectral mammography2018Inngår i: Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Berggren, Karl
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik. Philips Healthcare, S-17141 Solna, Sweden.
    Lundqvist, Mats
    Cederstrom, Bjorn
    Danielsson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Fredenberg, Erik
    Physical characterization of photon-counting tomosynthesis2015Konferansepaper (Fagfellevurdert)
    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.

  • 28.
    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 images1991Inngår i: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 181, nr 2, s. 469-474Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 29.
    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 Hemangiomas1990Inngår i: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 177, s. P228-Artikkel i tidsskrift (Fagfellevurdert)
  • 30. Blystad, I
    et al.
    Håkansson, I
    Tisell, A
    Ernerudh, J
    Smedby, Örjan
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Medicinsk bildbehandling och visualisering. Linköping University.
    Lundberg, P
    Larsson, E-M
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2015Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959XArtikkel i tidsskrift (Fagfellevurdert)
    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.

  • 31.
    Bokrantz, Rasmus
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori. RaySearch Laboratories, Sweden.
    Miettinen, Kaisa
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori. University of Jyväskylä, Finland.
    Projections onto the Pareto surface in multicriteria radiation therapy optimization2015Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 42, nr 10, s. 5862-5870Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To eliminate or reduce the error to Pareto optimality that arises in Pareto surface navigation when the Pareto surface is approximated by a small number of plans. Methods: The authors propose to project the navigated plan onto the Pareto surface as a postprocessing step to the navigation. The projection attempts to find a Pareto optimal plan that is at least as good as or better than the initial navigated plan with respect to all objective functions. An augmented form of projection is also suggested where dose-volume histogram constraints are used to prevent that the projection causes a violation of some clinical goal. The projections were evaluated with respect to planning for intensity modulated radiation therapy delivered by step-and-shoot and sliding window and spot-scanned intensity modulated proton therapy. Retrospective plans were generated for a prostate and a head and neck case. Results: The projections led to improved dose conformity and better sparing of organs at risk (OARs) for all three delivery techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on average for the unconstrained form of the projection and by 2.0 Gy on average when dose-volume histogram constraints were used. No consistent improvements in target homogeneity were observed. Conclusions: There are situations when Pareto navigation leaves room for improvement in OAR sparing and dose conformity, for example, if the approximation of the Pareto surface is coarse or the problem formulation has too permissive constraints. A projection onto the Pareto surface can identify an inaccurate Pareto surface representation and, if necessary, improve the quality of the navigated plan.

  • 32.
    Bornefalk, Hans
    KTH, Skolan för teknikvetenskap (SCI), Fysik.
    Computer-aided detection and novel mammography imaging techniques2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents techniques constructed to aid the radiologists in detecting breast cancer, the second largest cause of cancer deaths for western women. In the first part of the thesis, a computer-aided detection (CAD) system constructed for the detection of stellate lesions is presented. Different segmentation methods and an attempt to incorporate contra-lateral information are evaluated.

    In the second part, a new method for evaluating such CAD systems is presented based on constructing credible regions for the number of false positive marks per image at a certain desired target sensitivity. This method shows that the resulting regions are rather wide and this explains some of the difficulties encountered by other researchers when trying to compare CAD algorithms on different data sets. In this part an attempt to model the clinical use of CAD as a second look is also made and it shows that applying CAD in sequence to the radiologist in a routine manner, without duly altering the decision criterion of the radiologist, might very well result in suboptimal operating points.

    Finally, in the third part two dual-energy imaging methods optimized for contrast-enhanced imaging of breast tumors are presented. The first is based on applying an electronic threshold to a photon-counting digital detector to discriminate between high- and low-energy photons. This allows simultaneous acquisition of the high- and low-energy images. The second method is based on the geometry of a scanned multi-slit system and also allows single-shot contrast-enhanced dual-energy mammography by filtering the x-ray beam that reaches different detector lines differently.

  • 33.
    Bornefalk, Hans
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk avbildning.
    Synthetic Hounsfield units from spectral CT data2012Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, nr 7, s. N83-N87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Beam-hardening-free synthetic images with absolute CT numbers that radiologists are used to can be constructed from spectral CT data by forming 'dichromatic' images after basis decomposition. The CT numbers are accurate for all tissues and the method does not require additional reconstruction. This method prevents radiologists from having to relearn new rules-of-thumb regarding absolute CT numbers for various organs and conditions as conventional CT is replaced by spectral CT. Displaying the synthetic Hounsfield unit images side-by-side with images reconstructed for optimal detectability for a certain task can ease the transition from conventional to spectral CT.

  • 34.
    Bornefalk, Hans
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk avbildning.
    XCOM intrinsic dimensionality for low-Z elements at diagnostic energies2012Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, nr 2, s. 654-657Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To determine the intrinsic dimensionality of linear attenuation coefficients (LACs) from XCOM for elements with low atomic number (Z = 1-20) at diagnostic x-ray energies (25-120 keV). H-0(q), the hypothesis that the space of LACs is spanned by q bases, is tested for various q-values. Methods: Principal component analysis is first applied and the LACs are projected onto the first q principal component bases. The residuals of the model values vs XCOM data are determined for all energies and atomic numbers. Heteroscedasticity invalidates the prerequisite of i.i.d. errors necessary for bootstrapping residuals. Instead wild bootstrap is applied, which, by not mixing residuals, allows the effect of the non-i.i.d residuals to be reflected in the result. Credible regions for the eigenvalues of the correlation matrix for the bootstrapped LAC data are determined. If subsequent credible regions for the eigenvalues overlap, the corresponding principal component is not considered to represent true data structure but noise. If this happens for eigenvalues l and l + 1, for any l <= q, H-0(q) is rejected. Results: The largest value of q for which H-0(q) is nonrejectable at the 5%-level is q = 4. This indicates that the statistically significant intrinsic dimensionality of low-Z XCOM data at diagnostic energies is four. Conclusions: The method presented allows determination of the statistically significant dimensionality of any noisy linear subspace. Knowledge of such significant dimensionality is of interest for any method making assumptions on intrinsic dimensionality and evaluating results on noisy reference data. For LACs, knowledge of the low-Z dimensionality might be relevant when parametrization schemes are tuned to XCOM data. For x-ray imaging techniques based on the basis decomposition method (Alvarez and Macovski, Phys. Med. Biol. 21, 733-744, 1976), an underlying dimensionality of two is commonly assigned to the LAC of human tissue at diagnostic energies. The finding of a higher statistically significant dimensionality thus raises the question whether a higher assumed model dimensionality (now feasible with the advent of multibin x-ray systems) might also be practically relevant, i.e., if better tissue characterization results can be obtained.

  • 35.
    Bornefalk, Hans
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk avbildning.
    Danielsson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk avbildning.
    Photon-counting spectral computed tomography using silicon strip detectors: a feasibility study2010Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, nr 7, s. 1999-2022Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We show how the spectral imaging framework should be modified to account for a high fraction of Compton interactions in low Z detector materials such as silicon. Using this framework, where deposited energies differ from actual photon energies, we compare the performance of a silicon strip detector, including the influence of scatter inside the detector and charge sharing but disregarding signal pileup, with an ideal energy integrating detector. We show that although the detection efficiency for silicon rapidly drops for the acceleration voltages encountered in clinical computed tomography practice, silicon detectors could perform on a par with ideal energy integrating detectors for routine imaging tasks. The use of spectrally sensitive detectors opens up the possibility for decomposition techniques such as k-edge imaging, and we show that the proposed modification of the spectral imaging framework is beneficial for such imaging tasks.

  • 36.
    Bornefalk, Hans
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Persson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Theoretical Comparison of the Iodine Quantification Accuracy of Two Spectral CT Technologies2014Inngår i: IEEE Transactions on Medical Imaging, ISSN 0278-0062, E-ISSN 1558-254X, Vol. 33, nr 2, s. 556-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We compare the theoretical limits of iodine quantification for the photon counting multibin and dual energy technologies. Dual energy systems by necessity have to make prior assumptions in order to quantify iodine. We explicitly allow the multibin system to make the same assumptions and also allow them to be wrong. We isolate the effect of technology from imperfections and implementation issues by assuming both technologies to be ideal, i.e., without scattered radiation, unity detection efficiency and perfect energy response functions, and by applying the Cramer-Rao lower bound methodology to assess the quantification accuracy. When priors are wrong the maximum likelihood estimates will be biased and the mean square error of the quantification error is a more appropriate figure of merit. The evaluation assumes identical X-ray spectra for both methodologies and for that reason a sensitivity analysis is performed with regard to the assumed X-ray spectrum. We show that when iodine is quantified over regions of interest larger than 6 cm, multibin systems benefit by independent estimation of three basis functions. For smaller regions of interest multibin systems can increase quantification accuracy by making the same prior assumptions as dual energy systems.

  • 37.
    Bornefalk, Hans
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Persson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Danielsson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Necessary forward model specification accuracy for basis material decomposition in spectral CT2014Inngår i: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, s. 90332I-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Material basis decomposition in the sinogram domain requires accurate knowledge of the forward model in spectral CT. Misspecifications over a certain limit will result in biased estimates and make quantum limited quantitative CT difficult. We present a method whereby users can determine the degree of allowed misspecification error in a spectral CT forward model, and still have quantification errors that are quantum limited.

  • 38.
    Brodén, Cyrus
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet.
    Olivecrona, Henrik
    Department of Molecular Medicine and Surgery, Karolinska Institutet.
    Maguire Jr., Gerald Q.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS, Radio Systems Laboratory (RS Lab).
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Zeleznik, Michael P.
    School of Computing, College of Engineering, University of Utah.
    Sköldenberg, Olof
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet.
    Accuracy and Precision of Three-Dimensional Low Dose CT Compared to Standard RSA in Acetabular Cups: An Experimental Study2016Inngår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikkel-id 5909741Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Purpose. The gold standard for detection of implant wear and migration is currently radiostereometry (RSA). The purpose of this study is to compare a three-dimensional computed tomography technique (3D CT) to standard RSA as an alternative technique for measuring migration of acetabular cups in total hip arthroplasty.

    Materials and Methods. With tantalum beads, we marked one cemented and one uncemented cup and mounted these on a similarly marked pelvic model. A comparison was made between 3D CT and standard RSA for measuring migration. Twelve repeated stereoradiographs and CT scans with double examinations in each position and gradual migration of the implants were made. Precision and accuracy of the 3D CT were calculated.

    Results. The accuracy of the 3D CT ranged between 0.07 and 0.32 mm for translations and 0.21 and 0.82° for rotation. The precision ranged between 0.01 and 0.09 mm for translations and 0.06 and 0.29° for rotations, respectively. For standard RSA, the precision ranged between 0.04 and 0.09 mm for translations and 0.08 and 0.32° for rotations, respectively. There was no significant difference in precision between 3D CT and standard RSA. The effective radiation dose of the 3D CT method, comparable to RSA, was estimated to be 0.33 mSv.

    Interpretation. Low dose 3D CT is a comparable method to standard RSA in an experimental setting.

  • 39.
    Brown, Lisa G.
    et al.
    IBM Thomas J. Watson Research Center and Columbia University.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Noz, Marilyn E.
    New York University.
    Landmark-based 3D fusion of SPECT and CT images1993Inngår i: Sensor fusion VI: 7-8 September 1993, Boston, Massachusetts / [ed] Paul S. Schenker, SPIE - International Society for Optical Engineering, 1993, Vol. 2059, s. 166-174Konferansepaper (Fagfellevurdert)
    Abstract [en]

    In this paper we present interactive visualization procedures for registration of SPECT and CT images based on landmarks. Because of the poor anatomic detail available in many SPECT images, registration of SPECT images with other modalities often requires the use of external markers. These markers may correspond to anatomic structures identifiable in the other modality image. In this work, we present a method to nonrigidly register SPECT and CT images based on automatic marker localization and interactive anatomic localization using 3D surface renderings of skin. The images are registered in 3D by fitting low order polynomials which are constrained to be near rigid. The method developed here exploits 3D information to attain greater accuracy and reduces the amount of time needed for expert interaction.

  • 40.
    Brudfors, Mikael
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC).
    Seitel, Alexander
    University of British Columbia.
    Rasoulian, Abtin
    University of British Columbia.
    Lasso, Andras
    Queens University, Canada.
    Lessoway, Victoria
    Woman's Hospital, Vancouver, Canada.
    Osborn, Jill
    St Pauls Hospital, Vancouver, Canada.
    Maki, Atsuto
    KTH, Skolan för datavetenskap och kommunikation (CSC), Datorseende och robotik, CVAP.
    Rohling, Robert
    University of British Columbia.
    Abolmaesumi, Purang
    University of British Columbia.
    Towards real-time, tracker-less 3D ultrasound guidance for spine anaesthesia2015Inngår i: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 10, nr 6, s. 855-865Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Epidural needle insertions and facet joint injections play an important role in spine anaesthesia. The main challenge of safe needle insertion is the deep location of the target, resulting in a narrow and small insertion channel close to sensitive anatomy. Recent approaches utilizing ultrasound (US) as a low-cost and widely available guiding modality are promising but have yet to become routinely used in clinical practice due to the difficulty in interpreting US images, their limited view of the internal anatomy of the spine, and/or inclusion of cost-intensive tracking hardware which impacts the clinical workflow. Methods: We propose a novel guidance system for spine anaesthesia. An efficient implementation allows us to continuously align and overlay a statistical model of the lumbar spine on the live 3D US stream without making use of additional tracking hardware. The system is evaluated in vivo on 12 volunteers. Results: The in vivo study showed that the anatomical features of the epidural space and the facet joints could be continuously located, at a volume rate of 0.5 Hz, within an accuracy of 3 and 7 mm, respectively. Conclusions: A novel guidance system for spine anaesthesia has been presented which augments a live 3D US stream with detailed anatomical information of the spine. Results from an in vivo study indicate that the proposed system has potential for assisting the physician in quickly finding the target structure and planning a safe insertion trajectory in the spine.

  • 41. Bucht, C.
    et al.
    Söderberg, P.
    Manneberg, Göran
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2009Inngår i: Ophthalmic Technologies XIX, SPIE - International Society for Optical Engineering, 2009, s. 716315-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor. Morphometry of the corneal endothelium is presently done by semi-automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development of fully automated analysis of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images. The digitally enhanced images of the corneal endothelium were transformed, using the fast Fourier transform (FFT). Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on images captured by CSM. The cell density obtained by the fully automated analysis was compared to the cell density obtained from classical, semiautomated analysis and a relatively large correlation was found.

  • 42. Bucht, C.
    et al.
    Söderberg, P.
    Manneberg, Göran
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2010Inngår i: Ophthalmic Technologies XX, SPIE - International Society for Optical Engineering, 2010, s. 75501E-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor of the corneal endothelium. Pathological conditions and physical trauma may threaten the endothelial cell density to such an extent that the optical property of the cornea and thus clear eyesight is threatened. Diagnosis of the corneal endothelium through morphometry is an important part of several clinical applications. Morphometry of the corneal endothelium is presently carried out by semi automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development and use of fully automated analysis of a very large range of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images, normalizing lights and contrasts. The digitally enhanced images of the corneal endothelium were Fourier transformed, using the fast Fourier transform (FFT) and stored as new images. Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on 292 images captured by CSM. The cell density obtained by the fully automated analysis was compared to the cell density obtained from classical, semiautomated analysis and a relatively large correlation was found.

  • 43.
    Bucht, Curry
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Söderberg, P.
    Manneberg, Göran
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    The impact of horizontal offset of the cornea during corneal specular microscopy2008Inngår i: Progr. Biomed. Opt. Imaging Proc. SPIE, 2008Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We are developing automated morphometric analysis of the corneal endothelium. Here, the general impact of horizontal offset of the cornea on morphometry was examined. Errors due to perspective during imaging with a Clinical Specular Microscope (CSM) were analyzed considering semi automated analysis software and fully automated Fourier analysis software. Methods: A mathematical model of the cornea was created. Trigonometry was applied to find the relationship between the horizontal offset of the cornea relative to the microscope objective, and the consecutive errors from perspective changes in the image. An experimental setup was created using a cornea made of polymethyl methacrylate (PMMA). The posterior surface of the PMMA cornea was horizontally marked. The PMMA cornea was placed in a holder. Difference in refractive index between real endothelium and aqueous humor was emulated using high refractive index liquid. Images with varying horizontal offset on the PMMA corneal posterior surface, along with their relative offset coordinates were captured, using CSM. Results: Experiments using controlled offset of the cornea in relation to its center estimated that analyzable images can be acquired within an interval of 1.26 mm, using central cornea sampling CSM. Because of refractive indices along with light scattering differences between the corneal tissue and PMMA , the 1.26 mm interval should be considered a first estimate for feasible CSM images. The effect of corneal endothelial offset during imaging with CSM or fully automated Fourier analysis should be considered.

  • 44.
    Böck, Michelle
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori. RaySearch Labs AB, Sweden.
    Eriksson, Kjell
    Forsgren, Anders
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori.
    Hardemark, Bjorn
    Toward robust adaptive radiation therapy strategies2017Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 44, nr 6, s. 2054-2065Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To set up a framework combining robust treatment planning with adaptive re-optimization in order to maintain high treatment quality, to respond to interfractional geometric variations and to identify those patients who will benefit the most from an adaptive fractionation schedule. Methods: The authors propose robust adaptive strategies based on stochastic minimax optimization for a series of simulated treatments on a one-dimensional patient phantom. The plan applied during the first fractions should be able to handle anticipated systematic and random errors. Information on the individual geometric variations is gathered at each fraction. At scheduled fractions, the impact of the measured errors on the delivered dose distribution is evaluated. For a patient having received a dose that does not satisfy specified plan quality criteria, the plan is re-optimized based on these individually measured errors. The re-optimized plan is then applied during subsequent fractions until a new scheduled adaptation becomes necessary. In this study, three different adaptive strategies are introduced and investigated. (a) In the first adaptive strategy, the measured systematic and random error scenarios and their assigned probabilities are updated to guide the robust re-optimization. (b) In the second strategy, the degree of conservativeness is adapted in response to the measured dose delivery errors. (c) In the third strategy, the uncertainty margins around the target are recalculated based on the measured errors. The simulated treatments are subjected to systematic and random errors that are either similar to the anticipated errors or unpredictably larger in order to critically evaluate the performance of these three adaptive strategies. Results: According to the simulations, robustly optimized treatment plans provide sufficient treatment quality for those treatment error scenarios similar to the anticipated error scenarios. Moreover, combining robust planning with adaptation leads to improved organ-at-risk protection. In case of unpredictably larger treatment errors, the first strategy in combination with at most weekly adaptation performs best at notably improving treatment quality in terms of target coverage and organ-at-risk protection in comparison with a non-adaptive approach and the other adaptive strategies. Conclusion: The authors present a framework that provides robust plan re-optimization or margin adaptation of a treatment plan in response to interfractional geometric errors throughout the fractionated treatment. According to the simulations, these robust adaptive treatment strategies are able to identify candidates for an adaptive treatment, thus giving the opportunity to provide individualized plans, and improve their treatment quality through adaptation. The simulated robust adaptive framework is a guide for further development of optimally controlled robust adaptive therapy models.

  • 45. Cai, Fuhong
    et al.
    He, Sailing
    KTH, Skolan för elektro- och systemteknik (EES), Elektroteknisk teori och konstruktion. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Electric field Monte Carlo simulation of focused stimulated emission depletion beam, radially and azimuthally polarized beams for in vivo deep bioimaging2014Inngår i: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, nr 1, s. 011022-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An electric field Monte Carlo method is used to study the focal spot of a stimulated emission depletion (STED) beam, radially and azimuthally polarized beams in a turbid medium as a function of the scattering coefficient. To consider the diffraction of light of the wave nature, the wavefront is decomposed into a set of secondary spherical subwaves according to the Huygens principle. From the simulation results, we can find that the STED beam can still form a doughnut focal spot inside the turbid medium. These simulation results are important for the feasibility study of STED microscopy for in vivo deep bioimaging. Similarly, the focal spot for an azimuthally polarized beam can also keep a doughnut spot at the focal plane in a turbid medium.

  • 46. Cai, Fuhong
    et al.
    He, Sailing
    KTH, Skolan för elektro- och systemteknik (EES), Elektroteknisk teori och konstruktion.
    Using graphics processing units to accelerate perturbation Monte Carlo simulation in a turbid medium2012Inngår i: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, nr 4, s. 040502-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report a fast perturbation Monte Carlo (PMC) algorithm accelerated by graphics processing units (CPU). The two-step PMC simulation [Opt. Lett. 36, 2095 (2011)] is performed by storing the seeds instead of the photon's trajectory, and thus the requirement in computer random-access memory (RAM) becomes minimal. The two-step PMC is extremely suitable for implementation onto CPU. In a standard simulation of spatially-resolved photon migration in the turbid media, the acceleration ratio between using GPU and using conventional CPU is about 1000. Furthermore, since in the two-step PMC algorithm one records the effective seeds, which is associated to the photon that reaches a region of interest in this letter, and then re-run the MC simulation based on the recorded effective seeds, radiative transfer equation (RTE) can be solved by two-step PMC not only with an arbitrary change in the absorption coefficient, but also with large change in the scattering coefficient.

  • 47.
    Carlsson, Fredrik
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori.
    Combining segment generation with direct step-and-shoot optimization in intensity-modulated radiation therapy2008Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, nr 9, s. 3828-3838Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A method for generating a sequence of intensity-modulated radiation therapy step-and-shoot plans with increasing number of segments is presented. The objectives are to generate high-quality plans with few, large and regular segments, and to make the planning process more intuitive. The proposed method combines segment generation with direct step-and-shoot optimization, where leaf positions and segment weights are optimized simultaneously. The segment generation is based on a column generation approach. The method is evaluated on a test suite consisting of five head-and-neck cases and five prostate cases, planned for delivery with an Elekta SLi accelerator. The adjustment of segment shapes by direct step-and-shoot optimization improves the plan quality compared to using fixed segment shapes. The improvement in plan quality when adding segments is larger for plans with few segments. Eventually, adding more segments contributes very little to the plan quality, but increases the plan complexity. Thus, the method provides a tool for controlling the number of segments and, indirectly, the delivery time. This can support the planner in finding a sound trade-off between plan quality and treatment complexity.

  • 48.
    Carlsson, Fredrik
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori.
    Forsgren, Anders
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Optimeringslära och systemteori.
    Iterative regularization in intensity-modulated radiation therapy optimization2006Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 33, nr 1, s. 225-234Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A common way to solve intensity-modulated radiation therapy (IMRT) optimization problems is to use a beamlet-based approach. The approach is usually employed in a three-step manner: first a beamlet-weight optimization problem is solved, then the fluence profiles are converted into stepand-shoot segments, and finally postoptimization of the segment weights is performed. A drawback of beamlet-based approaches is that beamlet-weight optimization problems are ill-conditioned and have to be regularized in order to produce smooth fluence profiles that are suitable for conversion. The purpose of this paper is twofold: first, to explain the suitability of solving beamlet-based IMRT problems by a BFGS quasi-Newton sequential quadratic programming method with diagonal initial Hessian estimate, and second, to empirically show that beamlet-weight optimization problems should be solved in relatively few iterations when using this optimization method. The explanation of the suitability is based on viewing the optimization method as an iterative regularization method. In iterative regularization, the optimization problem is solved approximately by iterating long enough to obtain a solution close to the optimal one, but terminating before too much noise occurs. Iterative regularization requires an optimization method that initially proceeds in smooth directions and makes rapid initial progress. Solving ten beamlet-based IMRT problems with dose-volume objectives and bounds on the beamlet-weights, we find that the considered optimization method fulfills the requirements for performing iterative regularization. After segment-weight optimization, the treatments obtained using 35 beamlet-weight iterations outperform the treatments obtained using 100 beamlet-weight iterations, both in terms of objective value and of target uniformity. We conclude that iterating too long may in fact deteriorate the quality of the deliverable plan.

  • 49. Cederström, B.
    et al.
    Fredenberg, E.
    Berggren, Karl
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik. Mammography Solutions, Philips, Sweden.
    Erhard, K.
    Danielsson, Mats
    KTH, Skolan för teknikvetenskap (SCI), Fysik, Medicinsk bildfysik.
    Wallis, M.
    Lesion characterization in spectral photon-counting tomosynthesis2017Inngår i: Medical Imaging 2017: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2017, Vol. 10132, artikkel-id 1013205Konferansepaper (Fagfellevurdert)
    Abstract [en]

    It has previously been shown that 2D spectral mammography can be used to discriminate between (likely benign) cystic and (potentially malignant) solid lesions in order to reduce unnecessary recalls in mammography. One limitation of the technique is, however, that the composition of overlapping tissue needs to be interpolated from a region surrounding the lesion. The purpose of this investigation was to demonstrate that lesion characterization can be done with spectral tomosynthesis, and to investigate whether the 3D information available in tomosynthesis can reduce the uncertainty from the interpolation of surrounding tissue. A phantom experiment was designed to simulate a cyst and a tumor, where the tumor was overlaid with a structure that made it mimic a cyst. In 2D, the two targets appeared similar in composition, whereas spectral tomosynthesis revealed the exact compositional difference. However, the loss of discrimination signal due to spread from the plane of interest was of the same strength as the reduction of anatomical noise. Results from a preliminary investigation on clinical tomosynthesis images of solid lesions yielded results that were consistent with the phantom experiments, but were still to some extent inconclusive. We conclude that lesion characterization is feasible in spectral tomosynthesis, but more data, as well as refinement of the calibration and discrimination algorithms, are needed to draw final conclusions about the benefit compared to 2D.

  • 50.
    Cederström, Björn
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Fysik.
    Fredenberg, Erik
    KTH, Skolan för teknikvetenskap (SCI), Fysik.
    The influence of anatomical noise on optimal beam quality in mammography2014Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, nr 12, s. 121903-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Beam-quality optimization in digital mammography traditionally considers detection of a target obscured by quantum noise in a homogeneous background. This does not correspond well to the clinical imaging task because real mammographic images contain a complex superposition of anatomical structures, resulting in anatomical noise that may dominate over quantum noise. The purpose of this paper is to assess the influence on optimal beam quality in mammography when anatomical noise is taken into account. Methods: The detectability of microcalcifications and masses was quantified using a theoretical ideal-observer model that included quantum noise as well as anatomical noise and a simplified model of a photon-counting mammography system. The outcome was experimentally verified using two types of simulated tissue phantoms. Results: The theoretical model showed that the detectability of tumors and microcalcifications behaves differently with respect to beam quality and dose. The results for small microcalcifications were similar to what traditional optimization methods yield, which is to be expected because quantum noise dominates over anatomical noise at high spatial frequencies. For larger tumors, however, low-frequency anatomical noise was the limiting factor. Because anatomical structure noise has similar energy dependence as tumor contrast, the optimal x-ray energy was found to be higher and the useful energy region was wider than traditional methods suggest. A simplified scalar model was able to capture this behavior using a fitted noise mixing parameter. The phantom measurements confirmed these theoretical results. Conclusions: It was shown that since quantum noise constitutes only a small fraction of the noise, the dose could be reduced substantially without sacrificing tumor detectability. Furthermore, when anatomical noise is included, the tube voltage can be increased well beyond what is conventionally considered optimal and used clinically, without loss of image quality. However, no such conclusions can be drawn for the more complex mammographic imaging task as a whole. (C) 2014 American Association of Physicists in Medicine.

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