Application of Magnetic Particle Imaging to Pulmonary Imaging Using Nebulized Magnetic Nanoparticles
ABSTRACT
Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist®). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day−1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.
Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist®). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day−1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.
KEYWORDS
Magnetic Particle Imaging, Pulmonary Imaging, Nebulized Magnetic Nanoparticles, Animal Experiments
Magnetic Particle Imaging, Pulmonary Imaging, Nebulized Magnetic Nanoparticles, Animal Experiments
Cite this paper
Nishimoto, K. , Mimura, A. , Aoki, M. , Banura, N. and Murase, K. (2015) Application of Magnetic Particle Imaging to Pulmonary Imaging Using Nebulized Magnetic Nanoparticles. Open Journal of Medical Imaging, 5, 49-55. doi: 10.4236/ojmi.2015.52008.
Nishimoto, K. , Mimura, A. , Aoki, M. , Banura, N. and Murase, K. (2015) Application of Magnetic Particle Imaging to Pulmonary Imaging Using Nebulized Magnetic Nanoparticles. Open Journal of Medical Imaging, 5, 49-55. doi: 10.4236/ojmi.2015.52008.
References
[1] Dames, P., Gleich, B., Flemmer, A., Hajek, K., Seidl, N., Wiekhorst, F., Eberbeck, D., Bittmann, I., Bergemann, C., Weyh, T., Trahms, L., Rosenecker, J. and Rudolph, C. (2007) Targeted Delivery of Magnetic Aerosol Droplets to the Lung. Nature Nanotechnology, 2, 495-499.
http://dx.doi.org/10.1038/nnano.2007.217 [2] Mikhaylov, G., Mikac, U., Magaeva, A.A., Itin, V.I., Naiden, E.P., Psakhye, I., Babes, L., Reinheckel, T., Peters, C., Zeiser, R., Bogyo, M., Turk, V., Psakhye, S.G., Turk, B. and Vasilieva, O. (2011) Ferri-Liposomesas an MRI-Visible Drug-Delivery System for Targeting Tumours and Their Microenvironment. Nature Nanotechnology, 6, 594-602.
http://dx.doi.org/10.1038/nnano.2011.112 [3] Stocke, N.A., Meenach, S.A., Arnold, S.M., Mansour, H.M. and Hilt, J.Z. (2015) Formulation and Characterization of Inhalable Magnetic Nanocomposite Microparticles (MnMs) for Targeted Pulmonary Delivery via Spray Drying. International Journal of Pharmaceutics, 479, 320-328.
http://dx.doi.org/10.1016/j.ijpharm.2014.12.050 [4] Kirch, J., Guenther, M., Doshi, N., Schaefer, U.F., Schneider, M., Mitragotri, S. and Lehr, C-M. (2012) Mucociliary Clearance of Micro- and Nanoparticles Is Independent of Size, Shape and Charge—An ex Vivo and in Silico Approach. Journal of Controlled Release, 159, 128-134.
http://dx.doi.org/10.1016/j.jconrel.2011.12.015 [5] Gleich, B. and Weizenecker, J. (2005) Tomographic Imaging Using the Nonlinear Response of Magnetic Particles. Nature, 435, 1214-1217.
http://dx.doi.org/10.1038/nature03808 [6] Goodwill, P.W., Konkle, J.J., Zheng, B., Saritas, E.U. and Conolly, S.M. (2012) Projection X-space Magnetic Particle Imaging. IEEE Transactions on Medical Imaging, 31, 1076-1085.
http://dx.doi.org/10.1109/TMI.2012.2185247 [7] Murase, K., Hiratsuka, S., Song, R. and Takeuchi, Y. (2014) Development of a System for Magnetic Particle Imaging Using Neodymium Magnets and Gradiometer. Japanese Journal of Applied Physics, 53, Article ID: 067001.
http://dx.doi.org/10.7567/JJAP.53.067001 [8] Murase, K., Song, R. and Hiratsuka, S. (2014) Magnetic Particle Imaging of Blood Coagulation. Applied Physics Letters, 104, Article ID: 252409.
http://dx.doi.org/10.1063/1.4885146 [9] Murase, K., Oonoki, J., Takata, H., Song, R., Angraini, A.,Ausanai, P. and Matsushita, T. (2011) Simulation and Experimental Studies on Magnetic Hyperthermia with Use of Superparamagnetic Iron Oxide Nanoparticles. Radiological Physics and Technology, 4, 194-202.
http://dx.doi.org/10.1007/s12194-011-0123-4 [10] Biederer, S., Knopp, T., Sattel, T.F., Ludtke-Buzug, K., Gleich, B., Weizenecker, J., Borgert, J. and Buzug, T.M. (2009) Magnetization Response Spectroscopy of Superparamagnetic Nanoparticles for Magnetic Particle Imaging. Journal of Physics D: Applied Physics, 42, Article ID: 205007.
http://dx.doi.org/10.1088/0022-3727/42/20/205007 [11] Markov, D.E., Boeve, H., Gleich, B., Borgert, J., Antonelli, A., Sfara, C. and Magnani, M. (2010) Human Erythrocytes as Nanoparticle Carriers for Magnetic Particle Imaging. Physics in Medicine and Biology, 55, 6461-6473.
http://dx.doi.org/10.1088/0031-9155/55/21/008 [12] Murase, K., Banura, N., Mimura, A. and Nishimoto, K. (2015) Simple and Practical Method for Correcting the Inhomogeneous Sensitivity of a Receiving Coil in Magnetic Particle Imaging. Japanese Journal of Applied Physics, 54, Article ID: 038001.
http://dx.doi.org/10.7567/JJAP.54.038001 [13] Nelder, J.A. and Mead, R. (1965) A Simplex Method for Function Minimization. The Computer Journal, 7, 308-313.
http://dx.doi.org/10.1093/comjnl/7.4.308 [14] Semmler-Behnke, M., Takenaka, S., Fertsch, S., Wenk, A., Seitz, J., Mayer, P., Oberdöster, G. and Kreyling, W.G. (2007) Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium. Environmental Health Perspectives, 115, 728-733.
http://dx.doi.org/10.1289/ehp.9685 [15] Semmler, M., Seitz, J., Erbe, F., Mayer, P., Heyder, J., Oberdörster, G. and Kreyling, W.G. (2004) Long-Term Clearance Kinetics of Inhaled Ultrafine Insoluble Iridium Particles from the Rat Lung, Including Transient Translocation into Secondary Organs. Inhalation Toxicology, 16, 453-459.
http://dx.doi.org/10.1080/08958370490439650 [16] Fleming, J.S., Quint, M., Bolt, L., Martonen, T.B. and Conway, J.H. (2006) Comparison of SPECT Aerosol Deposition Data with Twenty-Four-Hour Clearance Measurements. Journal of Aerosol Medicine, 19, 261-267.
http://dx.doi.org/10.1089/jam.2006.19.261 [17] Robson, M.D., Gatehouse, P.D., Bydder, M. and Bydder, G.M. (2003) Magnetic Resonance: An Introduction to Ultrashort TE (UTE) Imaging. Journal of Computer Assisted Tomography, 27, 825-846.
http://dx.doi.org/10.1097/00004728-200311000-00001 [18] Idiyatullin, D., Corum, C., Park, J.Y. and Garwood, M. (2006) Fast and Quiet MRI Using a Swept Radiofrequency. Journal of Magnetic Resonance, 181, 342-349.
http://dx.doi.org/10.1016/j.jmr.2006.05.014 [19] Zhang, J.J., Chamberlain, R., Etheridge, M., Idiyatullin, D., Corum, C., Bischof, J. and Garwood, M. (2014) Quantifying Iron-Oxide Nanoparticles at High Concentration Based on Longitudinal Relaxation Using a Three-dimensional SWIFT Look-Locker Sequence. Magnetic Resonance in Medicine, 71, 1982-1988.
http://dx.doi.org/10.1002/mrm.25181 [20] Hoopes, P.J., Petryk, A.A., Tate, J.A., Savellano, M.S., Strawbridge, R.R., Giustini, A.J., Stan, R.V., Gimi, B. and Garwood, M. (2013) Imaging and Modification of the Tumor Vascular Barrier for Improvement in Magnetic Nanoparticle Uptake and Hyperthermia Treatment Efficacy. Proceedings SPIE 8584, Energy-Based Treatment of Tissue and Assessment VII, 858403, San Francisco, 26 February 2013, 1-14.
http://dx.doi.org/10.1117/12.2008689 [21] Möller, W., Häußinger, K., Winkler-Heil, R., Stahlhofen, W., Meyer, T., Hofmann, W. and Heyder, J. (2004) Mucociliary and Long-Term Particle Clearance in the Airways of Healthy Nonsmoker Subjects. Journal of Applied Physiology, 97, 2200-2206.
http://dx.doi.org/10.1152/japplphysiol.00970.2003 [22] Plank, C. (2008) Nanomagnetosols: Magnetism Opens up New Perspectives for Targeted Aerosol Delivery to the Lung. Trends in Biotechnology, 26, 59-63.
http://dx.doi.org/10.1016/j.tibtech.2007.11.001
[1] Dames, P., Gleich, B., Flemmer, A., Hajek, K., Seidl, N., Wiekhorst, F., Eberbeck, D., Bittmann, I., Bergemann, C., Weyh, T., Trahms, L., Rosenecker, J. and Rudolph, C. (2007) Targeted Delivery of Magnetic Aerosol Droplets to the Lung. Nature Nanotechnology, 2, 495-499.
http://dx.doi.org/10.1038/nnano.2007.217 [2] Mikhaylov, G., Mikac, U., Magaeva, A.A., Itin, V.I., Naiden, E.P., Psakhye, I., Babes, L., Reinheckel, T., Peters, C., Zeiser, R., Bogyo, M., Turk, V., Psakhye, S.G., Turk, B. and Vasilieva, O. (2011) Ferri-Liposomesas an MRI-Visible Drug-Delivery System for Targeting Tumours and Their Microenvironment. Nature Nanotechnology, 6, 594-602.
http://dx.doi.org/10.1038/nnano.2011.112 [3] Stocke, N.A., Meenach, S.A., Arnold, S.M., Mansour, H.M. and Hilt, J.Z. (2015) Formulation and Characterization of Inhalable Magnetic Nanocomposite Microparticles (MnMs) for Targeted Pulmonary Delivery via Spray Drying. International Journal of Pharmaceutics, 479, 320-328.
http://dx.doi.org/10.1016/j.ijpharm.2014.12.050 [4] Kirch, J., Guenther, M., Doshi, N., Schaefer, U.F., Schneider, M., Mitragotri, S. and Lehr, C-M. (2012) Mucociliary Clearance of Micro- and Nanoparticles Is Independent of Size, Shape and Charge—An ex Vivo and in Silico Approach. Journal of Controlled Release, 159, 128-134.
http://dx.doi.org/10.1016/j.jconrel.2011.12.015 [5] Gleich, B. and Weizenecker, J. (2005) Tomographic Imaging Using the Nonlinear Response of Magnetic Particles. Nature, 435, 1214-1217.
http://dx.doi.org/10.1038/nature03808 [6] Goodwill, P.W., Konkle, J.J., Zheng, B., Saritas, E.U. and Conolly, S.M. (2012) Projection X-space Magnetic Particle Imaging. IEEE Transactions on Medical Imaging, 31, 1076-1085.
http://dx.doi.org/10.1109/TMI.2012.2185247 [7] Murase, K., Hiratsuka, S., Song, R. and Takeuchi, Y. (2014) Development of a System for Magnetic Particle Imaging Using Neodymium Magnets and Gradiometer. Japanese Journal of Applied Physics, 53, Article ID: 067001.
http://dx.doi.org/10.7567/JJAP.53.067001 [8] Murase, K., Song, R. and Hiratsuka, S. (2014) Magnetic Particle Imaging of Blood Coagulation. Applied Physics Letters, 104, Article ID: 252409.
http://dx.doi.org/10.1063/1.4885146 [9] Murase, K., Oonoki, J., Takata, H., Song, R., Angraini, A.,Ausanai, P. and Matsushita, T. (2011) Simulation and Experimental Studies on Magnetic Hyperthermia with Use of Superparamagnetic Iron Oxide Nanoparticles. Radiological Physics and Technology, 4, 194-202.
http://dx.doi.org/10.1007/s12194-011-0123-4 [10] Biederer, S., Knopp, T., Sattel, T.F., Ludtke-Buzug, K., Gleich, B., Weizenecker, J., Borgert, J. and Buzug, T.M. (2009) Magnetization Response Spectroscopy of Superparamagnetic Nanoparticles for Magnetic Particle Imaging. Journal of Physics D: Applied Physics, 42, Article ID: 205007.
http://dx.doi.org/10.1088/0022-3727/42/20/205007 [11] Markov, D.E., Boeve, H., Gleich, B., Borgert, J., Antonelli, A., Sfara, C. and Magnani, M. (2010) Human Erythrocytes as Nanoparticle Carriers for Magnetic Particle Imaging. Physics in Medicine and Biology, 55, 6461-6473.
http://dx.doi.org/10.1088/0031-9155/55/21/008 [12] Murase, K., Banura, N., Mimura, A. and Nishimoto, K. (2015) Simple and Practical Method for Correcting the Inhomogeneous Sensitivity of a Receiving Coil in Magnetic Particle Imaging. Japanese Journal of Applied Physics, 54, Article ID: 038001.
http://dx.doi.org/10.7567/JJAP.54.038001 [13] Nelder, J.A. and Mead, R. (1965) A Simplex Method for Function Minimization. The Computer Journal, 7, 308-313.
http://dx.doi.org/10.1093/comjnl/7.4.308 [14] Semmler-Behnke, M., Takenaka, S., Fertsch, S., Wenk, A., Seitz, J., Mayer, P., Oberdöster, G. and Kreyling, W.G. (2007) Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium. Environmental Health Perspectives, 115, 728-733.
http://dx.doi.org/10.1289/ehp.9685 [15] Semmler, M., Seitz, J., Erbe, F., Mayer, P., Heyder, J., Oberdörster, G. and Kreyling, W.G. (2004) Long-Term Clearance Kinetics of Inhaled Ultrafine Insoluble Iridium Particles from the Rat Lung, Including Transient Translocation into Secondary Organs. Inhalation Toxicology, 16, 453-459.
http://dx.doi.org/10.1080/08958370490439650 [16] Fleming, J.S., Quint, M., Bolt, L., Martonen, T.B. and Conway, J.H. (2006) Comparison of SPECT Aerosol Deposition Data with Twenty-Four-Hour Clearance Measurements. Journal of Aerosol Medicine, 19, 261-267.
http://dx.doi.org/10.1089/jam.2006.19.261 [17] Robson, M.D., Gatehouse, P.D., Bydder, M. and Bydder, G.M. (2003) Magnetic Resonance: An Introduction to Ultrashort TE (UTE) Imaging. Journal of Computer Assisted Tomography, 27, 825-846.
http://dx.doi.org/10.1097/00004728-200311000-00001 [18] Idiyatullin, D., Corum, C., Park, J.Y. and Garwood, M. (2006) Fast and Quiet MRI Using a Swept Radiofrequency. Journal of Magnetic Resonance, 181, 342-349.
http://dx.doi.org/10.1016/j.jmr.2006.05.014 [19] Zhang, J.J., Chamberlain, R., Etheridge, M., Idiyatullin, D., Corum, C., Bischof, J. and Garwood, M. (2014) Quantifying Iron-Oxide Nanoparticles at High Concentration Based on Longitudinal Relaxation Using a Three-dimensional SWIFT Look-Locker Sequence. Magnetic Resonance in Medicine, 71, 1982-1988.
http://dx.doi.org/10.1002/mrm.25181 [20] Hoopes, P.J., Petryk, A.A., Tate, J.A., Savellano, M.S., Strawbridge, R.R., Giustini, A.J., Stan, R.V., Gimi, B. and Garwood, M. (2013) Imaging and Modification of the Tumor Vascular Barrier for Improvement in Magnetic Nanoparticle Uptake and Hyperthermia Treatment Efficacy. Proceedings SPIE 8584, Energy-Based Treatment of Tissue and Assessment VII, 858403, San Francisco, 26 February 2013, 1-14.
http://dx.doi.org/10.1117/12.2008689 [21] Möller, W., Häußinger, K., Winkler-Heil, R., Stahlhofen, W., Meyer, T., Hofmann, W. and Heyder, J. (2004) Mucociliary and Long-Term Particle Clearance in the Airways of Healthy Nonsmoker Subjects. Journal of Applied Physiology, 97, 2200-2206.
http://dx.doi.org/10.1152/japplphysiol.00970.2003 [22] Plank, C. (2008) Nanomagnetosols: Magnetism Opens up New Perspectives for Targeted Aerosol Delivery to the Lung. Trends in Biotechnology, 26, 59-63.
http://dx.doi.org/10.1016/j.tibtech.2007.11.001