title: Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury.
abstract: Purpose To evaluate whether noninvasive molecular imaging technologies targeting myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and Methods The study was approved by the institutional animal care and use committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n = 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting MPO activity were performed after intravenous injection of MPO sensors (bis-5-hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid [DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively). Immunohistochemistry and flow cytometry were used to identify myeloid cells and neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay. Statistical analyses were performed by using nonparametric tests and the Pearson correlation coefficient. P < .05 was considered to indicate a significant difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24 hours after TAR. MR imaging confirmed the presence of ischemic lesions associated with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours after TAR (P = .0001). The number of motor neurons decreased substantially at 24 hours after TAR (P < .01), which correlated inversely with in vivo inflammatory changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily secreted by neutrophils, followed by lymphocyte antigen 6 complexhighmonocytes and/or macrophages. There were corresponding increased levels of proinflammatory cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO activity. Conclusion MPO is a suitable imaging biomarker for identifying and tracking inflammatory damage in the spinal cord after TAR in a mouse model.©RSNA, 2016 Online supplemental material is available for this article.
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Hassan
authors: H
authors: Albadawi
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: John W
authors: JW
authors: Chen
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Rahmi
authors: http://orcid.org/0000-0003-4984-1778
authors: R
authors: Oklu
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Yue
authors: Y
authors: Wu
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Gregory
authors: G
authors: Wojtkiewicz
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Benjamin
authors: B
authors: Pulli
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: John D
authors: JD
authors: Milner
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Richard P
authors: RP
authors: Cambria
authors: From the Department of Surgery, Division of Vascular and Endovascular Surgery (H.A., J.D.M., R.P.C., M.T.W.), and Center for System Biology and Institute for Innovation in Imaging, Department of Radiology (J.W.C., Y.W., G.W., B.P.), Massachusetts General Hospital, Harvard Medical School, 70 Blossom St, Edwards 301, Boston, MA 02114; and Department of Radiology, Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, Ariz (R.O.).
authors: Michael T
authors: MT
authors: Watkins
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging* / Q000293:injuries; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging; D009187:Myelitis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009195:Peroxidase / Q000097:blood; D000072078:Positron Emission Tomography Computed Tomography; D015427:Reperfusion Injury / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D009195:Peroxidase