title: Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke.
abstract: Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [(18)F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [(18)F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation.
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Zinnhardt
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Paris Centre de Recherche Cardiovasculaire (PARC), Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.affiliation: Department of Clinical Radiology of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Wachsmuth
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vrachimis
authors.affiliation: Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Breyholz
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faust
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.affiliation: Department of Clinical Radiology of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Faber
authors.affiliation: Service Hospitalier Frédéric Joliot, Institut d'Imagerie BioMédicale, CEA, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Pappata
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.affiliation: Paris Centre de Recherche Cardiovasculaire (PARC), Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Department of Nuclear Medicine of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.|Institute of Physiological Chemistry and Pathobiochemistry, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Sorokin
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kuhlmann
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms University Münster, Münster, Germany.|Department of Geriatrics, Johanniter Hospital, Evangelische Kliniken, Bonn, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000000981:diagnostic imaging* / Q000473:pathology; D064847:Multimodal Imaging / Q000379:methods*; D059906:Neuroimaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D020521:Stroke / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000473:pathology; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D020782:Matrix Metalloproteinases