- Email: [email protected]
“γ-eye”: A paradigm shift in scintigraphic mouse imaging
Abstracts / Physica Medica 32 (2016) 222–250
are introduced. Another marker is attached to the outer end of the needle. Once the device is mounted, a spherical coordinate system is built. Two in-house software programs have been developed to obtain the coordinates of the tumour tissue respect to the frame and to assess the correct position of the needle tip. Results. For testing purposes of the prototype an alginate tumour phantom was built in which a sphere of 10 mm of diameter and an activity concentration of 4:1 with respect the background is settled. After all biopsy punctures we found the needle tip inside the tumour, with an accuracy of less than 5 mm with respect the center of the target. Conclusion. A first prototype has been built and tested successfully. Anyway some improvements should be made and more trials have to be done to completely characterize the device. Disclosure. The authors have applied, with Osakidetza SVS, for a patent for the device described in this publication (P201531185, Oficina Española de Patentes y Marcas, Ministerio de Industria, Energía y Turismo).
http://dx.doi.org/10.1016/j.ejmp.2016.07.504
ON A NEW MECHANISM ON c-RAY ATTENUATION STRENGTHENED BY NEW DATA E. Adamides *, A. Kavadjiklis, S.K. Koutroubas, N. Moshonas, A. Tzedakis AEI Piraeus TT, Petrou Ralli and Thivon, Egaleo, Greece Corresponding author.
⇑
Introduction. We extended our previous detailed c-ray attenuation measurements of 60Co c rays in Pb and Fe to include also Cu, Hg, Al and H2O. Purpose. To introduce a new mechanism on c-ray attenuation in matter. Materials and methods. 60Co radiation source, slices of the absorbers and a Geiger Müller detector counter in broad and thin beam geometries. Experiments. We performed detailed measurements of the detected radiation versus the thickness of the absorber and in parallel Monte Carlo simulations for each experiment. Results. Monte-Carlo calculations were in qualitative agreement with experiment but quantitatively predicted systematically more radiation at the target. We related the differences with the parameters Ec and Zeff of the photoelectric absorption cross section which guided us to propose a new mechanism on the absorption of c rays in matter. The c radiation creates a huge number of electrons and ions passing through the absorber which form a steady state plasma condition increasing slightly the parameters Eb and Zeff of the lattice which in turn can increase measurably the photoelectric absorption thus restoring the agreement between Monte Carlo calculations and experiment. Conclusion. Based on our large set of data which included absorbers in a wide range of Zeff we strengthened the need for a new mechanism on c-ray absorption in matter.
http://dx.doi.org/10.1016/j.ejmp.2016.07.505
THE IMPACT OF CELL PROLIFERATION AND RADIONUCLIDE UPTAKE RATE IN RADIO-IMMUNOTHERAPY Martin Šefl a,b,c,*, Ioanna Kyriakou c, Dimitris Emfietzoglou c a
Department of Radiation Dosimetry, Nuclear Physics Institute, Academy of Sciencese of the Czech Republic, 180 00 Prague, Czech Republic
241
b Department of Dosimetry and Application of Ionizing Radiation, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, 110 00 Prague, Czech Republic c Medical Physics Laboratory, University of Ioannina Medical School, 45110 Ioannina, Greece ⇑ Corresponding author.
Purpose. The instantaneous-uptake model of O’Donoghue [”The impact of tumor cell proliferation in radio-immunotherapy”, Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is being extended to arbitrary uptake rates of the radiopharmaceutical in tumor cells. Methods. The time derivative of the survival curve is examined and an expression for the minimum of the surviving fraction is deduced along with a new expression for the biological effective dose (BED). Surviving fractions are calculated over a clinically relevant parameter range to establish general trends. Results. Results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h-1 and a biological clearance half-life of 7 days. Cell doubling time equals 2 days. The exponential-uptake rate of the radiopharmaceutical by the targeted cells appears to have a considerable effect on the survival of a proliferating cell population (even for uptake half-times of only a few hours) and thence might need to be considered in the radiobiological models of tumor cellkill in radio-immunotherapy. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for radionuclides with higher half-life. Moreover, the sensitivity of the cell survival on the uptake was found to be higher for the tumor cells with higher radio-sensitivity. Conclusion. Neglecting an uptake phase may result in a considerable overestimation of cell kill. http://dx.doi.org/10.1016/j.ejmp.2016.07.506
‘‘C-EYE”: A PARADIGM SHIFT IN SCINTIGRAPHIC MOUSE IMAGING Georgiou Maria a,*, Papadimitroulas Panagiotis a, Fysikopoulos Eleftherios a, Mikropoulos Konstantinos a, Loudos George b a
BET Solutions, R & D, Athens, Greece Technological Educational Institute of Athens, Biomedical Engineering, Athens, Greece ⇑ Corresponding author. b
Introduction-purpose. Small animal imaging has been well proven as a robust tool to non-invasively study the biodistribution of various biomolecules. A number of imaging systems are commercially available but with high purchase and maintenance costs. For this reason, we present the ‘‘c-eye”, a dedicated c-camera suitable for in-vivo scintigraphic molecular imaging. The ‘‘c-eye” is a unique benchtop system with 5 10 cm2 field-of-view for whole-body mouse imaging. Materials & methods. The ‘‘c-eye” is based on two PositionSensiti vePhotomultiplierTubes H8500 coupled to a CsINa pixelated scintillator and a low energy parallel hexagonal hole collimator. The external dimensions of the entire system, including all required electronics, are 45 30 15 cm3. All studies can be stored as raw data and in DICOM format and are handled through a DatabaseManager. The software supports a real-time viewer mode with selectable time frame and a post-processing mode, where various tools are adapted. Results. The spatial resolution was measured 2 mm @0 mm, the energy resolution for the 140 keV is 26% and the maximum sensitivity of the system is 200 cps/MBq. The quantification ability was
242
Abstracts / Physica Medica 32 (2016) 222–250
assessed using a phantom of 4 tubes filled with 99mTc solution with different activities. Our results demonstrate accurate quantitative information even for 10 s scans. The system was tested using a mouse injected with 99mTc-MDP for bone imaging, a mouse injected with 99mTc-DMSA for kidneys imaging and finally a mouse injected with 99mTc-MIBI for heart imaging. Conclusion. A new low-cost system, suitable for scintigraphic mouse imaging has been developed and evaluated using phantoms and small animals. Its dimensions and cost make it a unique solution for groups activated in the field of small animal nuclear imaging. http://dx.doi.org/10.1016/j.ejmp.2016.07.507
AUTOMATIC BONE MARROW SEGMENTATION FOR PETCT IMAGING IN MULTIPLE MYELOMA P. Leydon a,*, M. O’Connell b, D. Greene c, K. Curran a a Complex & Adaptive Systems Laboratory, University College Dublin, Ireland b The Mater Private Dublin, Ireland c Insight: Centre for Data Analytics, University College Dublin, Ireland ⇑ Corresponding author.
Introduction. Multiple myeloma (MM) is a malignant hematologic disorder characterized by bone marrow infiltration with neoplastic plasma cells. Approximately 10% of all hematologic cancers are related to MM. Whole-body 18F-FDG PETCT is an extremely useful imaging tool for the assessment of patients with MM. The novel approach developed in this research automatically segments bone marrow regions of interest on both the PET and CT datasets. Purpose. To automate bone marrow segmentation in PET. Materials and methods. Firstly, affine linear transforms are applied to the PET dataset and it is aligned to the CT images. Next, a binary mask is created based on a pixel threshold value of cortical bone. A series of image processing steps are performed to remove noise and fill gaps that correspond to bone marrow locations. This process results in a binary mask relating to bone marrow only which can then be applied to the registered PET dataset. Conclusion. The proposed method offers a fully automated and completely objective approach for segmentation of anatomical regions relating to bone marrow. With further development, this method could be used to evaluate clinical images in order to develop a database of PETCT images against which quantitative statistical comparisons between patients with normal bone marrow metabolism and those with myeloma can be made, establishing a baseline against which future scans may be referenced. In cases where the suspicion of myeloma exists, the tools could be used to support the diagnosis of the disease, and may be useful in staging of the disease in cases positive for myeloma. http://dx.doi.org/10.1016/j.ejmp.2016.07.508
CELLULAR AND SUBCELLULAR DOSIMETRY OF RADIOISOTOPES USED FOR PET IMAGING Hocine Nora a,*, Faivre Lionel b, Sarda-Mantel Laure c a
Institut de Radioprotection et de Sûreté Nucléaire, France INSERM, APHP, France c INSERM, IUH, Paris Diderot University, APHP, France ⇑ Corresponding author. b
Introduction. PET/CT imaging may be a useful method to follow and monitor the homing of hematopoietic stem and progenitor cells (HSPC) after HSPC injection in mice. To improve the method of HSPC
radiolabelling and to select the best radioisotopes for this technique a cellular dosimetry is required. Purpose. This early research work is focused on using Monte Carlo code to estimate the dose at cellular and subcellular levels for 3 radioisotopes used in PET: F-18, Cu-64 and Zr-89. Methods. S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo (MC) simulations are carried out, nucleus (N), Cytoplasm (Cy), Cellular surface (CS) and radiation source were simulated. The cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 4 to 8 lm. Different source-to-target combinations are considered namely nucleus to nucleus (N N), cytoplasm-to-nucleus (N Cy) and cell surface-to-nucleus (N CS). The S-values (in Gy/Bq.s) were calculated for cell nucleus and cellular surface distribution of radioactivity. Results. A comparison of MC results with the MIRD values for studied configurations are carried out for the radioisotopes studied. We generally find the largest deviations with MIRD for geometries where the target is at some distance from the source and, therefore, the results depend more strongly upon the plasmic membrane penetration ability of particles. http://dx.doi.org/10.1016/j.ejmp.2016.07.509
INVERSION OF THE ATTENUATED RADON TRANSFORM USING CUBIC SPLINES Nicholas E. Protonotarios a,b,*, Athanassios S. Fokas a,c, Anastasios Gaitanis d, George A. Kastis a a
Research Center of Mathematics, Academy of Athens, Greece Department of Mathematics, National Technical University of Athens, Greece c Department of Applied Mathematics and Theoretical Physics, University of Cambridge, UK d Biomedical Research Foundation of the Academy of Athens, Greece ⇑ Corresponding author. b
Introduction. The mathematics of single photon emission computed tomography (SPECT) involve the inversion of a certain integral, namely the attenuated Radon transform. This integral is stored in the form of the so-called attenuated sinogram. Purpose. By modifying the original formulation introduced by one of the authors in 2006, we have presented a slightly different formulation of the Inverse Attenuated Radon Transform (IART), which we refer to as attenuated Spline Reconstruction Technique (aSRT). The purpose of this study is to evaluate aSRT using simulated SPECT/CT phantoms and compare it with the industry standard, filtered backprojection (FBP). Materials and methods. We have rederived the analytic formula of the IART, which involves the Hilbert transform of the attenuation correction coefficient as well as of two functions of the attenuated sinogram. For the numerical implementation of these Hilbert transforms we have employed an approximation of custom-made third degree piecewise polynomials, namely cubic splines. Relevant sinograms were generated in STIR (Software for Tomographic Imaging Reconstruction) and were acquired for 30, 60, 120, 180, and 360 projections over 360 degrees. Comparisons with FBP were evaluated using contrast and bias. Results. Our numerical tests suggest that the new technique can efficiently produce accurate reconstructions for real phantoms. Conclusion. aSRT provides an alternative to FBP, which incorporates the attenuation correction within the algorithm itself. G.A. Kastis acknowledges the financial support of the ”Alexander S. Onassis Public Benefit Foundation” under grant No. R ZL 001-0. Furthermore, this work was partially supported by the research pro-
are introduced. Another marker is attached to the outer end of the needle. Once the device is mounted, a spherical coordinate system is built. Two in-house software programs have been developed to obtain the coordinates of the tumour tissue respect to the frame and to assess the correct position of the needle tip. Results. For testing purposes of the prototype an alginate tumour phantom was built in which a sphere of 10 mm of diameter and an activity concentration of 4:1 with respect the background is settled. After all biopsy punctures we found the needle tip inside the tumour, with an accuracy of less than 5 mm with respect the center of the target. Conclusion. A first prototype has been built and tested successfully. Anyway some improvements should be made and more trials have to be done to completely characterize the device. Disclosure. The authors have applied, with Osakidetza SVS, for a patent for the device described in this publication (P201531185, Oficina Española de Patentes y Marcas, Ministerio de Industria, Energía y Turismo).
http://dx.doi.org/10.1016/j.ejmp.2016.07.504
ON A NEW MECHANISM ON c-RAY ATTENUATION STRENGTHENED BY NEW DATA E. Adamides *, A. Kavadjiklis, S.K. Koutroubas, N. Moshonas, A. Tzedakis AEI Piraeus TT, Petrou Ralli and Thivon, Egaleo, Greece Corresponding author.
⇑
Introduction. We extended our previous detailed c-ray attenuation measurements of 60Co c rays in Pb and Fe to include also Cu, Hg, Al and H2O. Purpose. To introduce a new mechanism on c-ray attenuation in matter. Materials and methods. 60Co radiation source, slices of the absorbers and a Geiger Müller detector counter in broad and thin beam geometries. Experiments. We performed detailed measurements of the detected radiation versus the thickness of the absorber and in parallel Monte Carlo simulations for each experiment. Results. Monte-Carlo calculations were in qualitative agreement with experiment but quantitatively predicted systematically more radiation at the target. We related the differences with the parameters Ec and Zeff of the photoelectric absorption cross section which guided us to propose a new mechanism on the absorption of c rays in matter. The c radiation creates a huge number of electrons and ions passing through the absorber which form a steady state plasma condition increasing slightly the parameters Eb and Zeff of the lattice which in turn can increase measurably the photoelectric absorption thus restoring the agreement between Monte Carlo calculations and experiment. Conclusion. Based on our large set of data which included absorbers in a wide range of Zeff we strengthened the need for a new mechanism on c-ray absorption in matter.
http://dx.doi.org/10.1016/j.ejmp.2016.07.505
THE IMPACT OF CELL PROLIFERATION AND RADIONUCLIDE UPTAKE RATE IN RADIO-IMMUNOTHERAPY Martin Šefl a,b,c,*, Ioanna Kyriakou c, Dimitris Emfietzoglou c a
Department of Radiation Dosimetry, Nuclear Physics Institute, Academy of Sciencese of the Czech Republic, 180 00 Prague, Czech Republic
241
b Department of Dosimetry and Application of Ionizing Radiation, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, 110 00 Prague, Czech Republic c Medical Physics Laboratory, University of Ioannina Medical School, 45110 Ioannina, Greece ⇑ Corresponding author.
Purpose. The instantaneous-uptake model of O’Donoghue [”The impact of tumor cell proliferation in radio-immunotherapy”, Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is being extended to arbitrary uptake rates of the radiopharmaceutical in tumor cells. Methods. The time derivative of the survival curve is examined and an expression for the minimum of the surviving fraction is deduced along with a new expression for the biological effective dose (BED). Surviving fractions are calculated over a clinically relevant parameter range to establish general trends. Results. Results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h-1 and a biological clearance half-life of 7 days. Cell doubling time equals 2 days. The exponential-uptake rate of the radiopharmaceutical by the targeted cells appears to have a considerable effect on the survival of a proliferating cell population (even for uptake half-times of only a few hours) and thence might need to be considered in the radiobiological models of tumor cellkill in radio-immunotherapy. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for radionuclides with higher half-life. Moreover, the sensitivity of the cell survival on the uptake was found to be higher for the tumor cells with higher radio-sensitivity. Conclusion. Neglecting an uptake phase may result in a considerable overestimation of cell kill. http://dx.doi.org/10.1016/j.ejmp.2016.07.506
‘‘C-EYE”: A PARADIGM SHIFT IN SCINTIGRAPHIC MOUSE IMAGING Georgiou Maria a,*, Papadimitroulas Panagiotis a, Fysikopoulos Eleftherios a, Mikropoulos Konstantinos a, Loudos George b a
BET Solutions, R & D, Athens, Greece Technological Educational Institute of Athens, Biomedical Engineering, Athens, Greece ⇑ Corresponding author. b
Introduction-purpose. Small animal imaging has been well proven as a robust tool to non-invasively study the biodistribution of various biomolecules. A number of imaging systems are commercially available but with high purchase and maintenance costs. For this reason, we present the ‘‘c-eye”, a dedicated c-camera suitable for in-vivo scintigraphic molecular imaging. The ‘‘c-eye” is a unique benchtop system with 5 10 cm2 field-of-view for whole-body mouse imaging. Materials & methods. The ‘‘c-eye” is based on two PositionSensiti vePhotomultiplierTubes H8500 coupled to a CsINa pixelated scintillator and a low energy parallel hexagonal hole collimator. The external dimensions of the entire system, including all required electronics, are 45 30 15 cm3. All studies can be stored as raw data and in DICOM format and are handled through a DatabaseManager. The software supports a real-time viewer mode with selectable time frame and a post-processing mode, where various tools are adapted. Results. The spatial resolution was measured 2 mm @0 mm, the energy resolution for the 140 keV is 26% and the maximum sensitivity of the system is 200 cps/MBq. The quantification ability was
242
Abstracts / Physica Medica 32 (2016) 222–250
assessed using a phantom of 4 tubes filled with 99mTc solution with different activities. Our results demonstrate accurate quantitative information even for 10 s scans. The system was tested using a mouse injected with 99mTc-MDP for bone imaging, a mouse injected with 99mTc-DMSA for kidneys imaging and finally a mouse injected with 99mTc-MIBI for heart imaging. Conclusion. A new low-cost system, suitable for scintigraphic mouse imaging has been developed and evaluated using phantoms and small animals. Its dimensions and cost make it a unique solution for groups activated in the field of small animal nuclear imaging. http://dx.doi.org/10.1016/j.ejmp.2016.07.507
AUTOMATIC BONE MARROW SEGMENTATION FOR PETCT IMAGING IN MULTIPLE MYELOMA P. Leydon a,*, M. O’Connell b, D. Greene c, K. Curran a a Complex & Adaptive Systems Laboratory, University College Dublin, Ireland b The Mater Private Dublin, Ireland c Insight: Centre for Data Analytics, University College Dublin, Ireland ⇑ Corresponding author.
Introduction. Multiple myeloma (MM) is a malignant hematologic disorder characterized by bone marrow infiltration with neoplastic plasma cells. Approximately 10% of all hematologic cancers are related to MM. Whole-body 18F-FDG PETCT is an extremely useful imaging tool for the assessment of patients with MM. The novel approach developed in this research automatically segments bone marrow regions of interest on both the PET and CT datasets. Purpose. To automate bone marrow segmentation in PET. Materials and methods. Firstly, affine linear transforms are applied to the PET dataset and it is aligned to the CT images. Next, a binary mask is created based on a pixel threshold value of cortical bone. A series of image processing steps are performed to remove noise and fill gaps that correspond to bone marrow locations. This process results in a binary mask relating to bone marrow only which can then be applied to the registered PET dataset. Conclusion. The proposed method offers a fully automated and completely objective approach for segmentation of anatomical regions relating to bone marrow. With further development, this method could be used to evaluate clinical images in order to develop a database of PETCT images against which quantitative statistical comparisons between patients with normal bone marrow metabolism and those with myeloma can be made, establishing a baseline against which future scans may be referenced. In cases where the suspicion of myeloma exists, the tools could be used to support the diagnosis of the disease, and may be useful in staging of the disease in cases positive for myeloma. http://dx.doi.org/10.1016/j.ejmp.2016.07.508
CELLULAR AND SUBCELLULAR DOSIMETRY OF RADIOISOTOPES USED FOR PET IMAGING Hocine Nora a,*, Faivre Lionel b, Sarda-Mantel Laure c a
Institut de Radioprotection et de Sûreté Nucléaire, France INSERM, APHP, France c INSERM, IUH, Paris Diderot University, APHP, France ⇑ Corresponding author. b
Introduction. PET/CT imaging may be a useful method to follow and monitor the homing of hematopoietic stem and progenitor cells (HSPC) after HSPC injection in mice. To improve the method of HSPC
radiolabelling and to select the best radioisotopes for this technique a cellular dosimetry is required. Purpose. This early research work is focused on using Monte Carlo code to estimate the dose at cellular and subcellular levels for 3 radioisotopes used in PET: F-18, Cu-64 and Zr-89. Methods. S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo (MC) simulations are carried out, nucleus (N), Cytoplasm (Cy), Cellular surface (CS) and radiation source were simulated. The cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 4 to 8 lm. Different source-to-target combinations are considered namely nucleus to nucleus (N N), cytoplasm-to-nucleus (N Cy) and cell surface-to-nucleus (N CS). The S-values (in Gy/Bq.s) were calculated for cell nucleus and cellular surface distribution of radioactivity. Results. A comparison of MC results with the MIRD values for studied configurations are carried out for the radioisotopes studied. We generally find the largest deviations with MIRD for geometries where the target is at some distance from the source and, therefore, the results depend more strongly upon the plasmic membrane penetration ability of particles. http://dx.doi.org/10.1016/j.ejmp.2016.07.509
INVERSION OF THE ATTENUATED RADON TRANSFORM USING CUBIC SPLINES Nicholas E. Protonotarios a,b,*, Athanassios S. Fokas a,c, Anastasios Gaitanis d, George A. Kastis a a
Research Center of Mathematics, Academy of Athens, Greece Department of Mathematics, National Technical University of Athens, Greece c Department of Applied Mathematics and Theoretical Physics, University of Cambridge, UK d Biomedical Research Foundation of the Academy of Athens, Greece ⇑ Corresponding author. b
Introduction. The mathematics of single photon emission computed tomography (SPECT) involve the inversion of a certain integral, namely the attenuated Radon transform. This integral is stored in the form of the so-called attenuated sinogram. Purpose. By modifying the original formulation introduced by one of the authors in 2006, we have presented a slightly different formulation of the Inverse Attenuated Radon Transform (IART), which we refer to as attenuated Spline Reconstruction Technique (aSRT). The purpose of this study is to evaluate aSRT using simulated SPECT/CT phantoms and compare it with the industry standard, filtered backprojection (FBP). Materials and methods. We have rederived the analytic formula of the IART, which involves the Hilbert transform of the attenuation correction coefficient as well as of two functions of the attenuated sinogram. For the numerical implementation of these Hilbert transforms we have employed an approximation of custom-made third degree piecewise polynomials, namely cubic splines. Relevant sinograms were generated in STIR (Software for Tomographic Imaging Reconstruction) and were acquired for 30, 60, 120, 180, and 360 projections over 360 degrees. Comparisons with FBP were evaluated using contrast and bias. Results. Our numerical tests suggest that the new technique can efficiently produce accurate reconstructions for real phantoms. Conclusion. aSRT provides an alternative to FBP, which incorporates the attenuation correction within the algorithm itself. G.A. Kastis acknowledges the financial support of the ”Alexander S. Onassis Public Benefit Foundation” under grant No. R ZL 001-0. Furthermore, this work was partially supported by the research pro-