From cartoon to real time MRI: in vivo monitoring of phagocyte migration in mouse brain.
Recent studies have demonstrated that immune cells play an important role in the pathogenesis of many neurological conditions. Immune cells constantly survey the brain microvasculature for irregularities in levels of factors that signal homeostasis. Immune responses are initiated when necessary, resulting in mobilisation of the microglial cells resident in the central nervous system (CNS) and/or of infiltrating peripheral cells. However, little is known about the kinetics of immune cells in healthy and diseased CNS, because it is difficult to perform long-term visualisation of cell motility in live tissue with minimal invasion. Here, we describe highly sensitive in vivo MRI techniques for sequential monitoring of cell migration in the CNS at the single-cell level. We show that MRI combined with intravenous administration of super-paramagnetic particles of iron oxide (SPIO) can be used to monitor the transmigration of peripheral phagocytes into healthy or LPS-treated mouse brains. We also demonstrate dynamic cell migration in live animal brains with time-lapse MRI videos. Time-lapse MRI was used to visualise and track cells with low motility in a control mouse brain. High-sensitivity MRI cell tracking using SPIO offers new insights into immune cell kinetics in the brain and the mechanisms of CNS homeostasis.
1] Biofunctional Imaging, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan [2] Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yuki
Y
Mori
1] Biofunctional Imaging, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan [2] Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ting
T
Chen
Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan.
Tetsuya
T
Fujisawa
Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan.
Syoji
S
Kobashi
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Kohji
K
Ohno
Biotechnology Development Laboratories, Kaneka Corporation, 1-8 Takasago-cho Miyamae-cho, Takasago, Hyogo 676-8688, Japan.
Shinichi
S
Yoshida
Biotechnology Development Laboratories, Kaneka Corporation, 1-8 Takasago-cho Miyamae-cho, Takasago, Hyogo 676-8688, Japan.
Yoshiyuki
Y
Tago
Single Molecule Imaging, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yutaka
Y
Komai
Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan.
Yutaka
Y
Hata
1] Biofunctional Imaging, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan [2] Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshichika
Y
Yoshioka
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D058948:Cell Tracking / Q000295:instrumentation / Q000379:methods*; D003287:Contrast Media / Q000008:administration & dosage; D005290:Ferric Compounds / Q000008:administration & dosage; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D059010:Single-Cell Analysis / Q000295:instrumentation / Q000379:methods*; D059008:Time-Lapse Imaging; D014741:Video Recording
D003287:Contrast Media; D005290:Ferric Compounds; D008070:Lipopolysaccharides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C000499:ferric oxide