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Published on: December 31, 2017
Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury
Hassan Albadawi1, John W Chen1, Rahmi Oklu1
1From 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.).
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 complexhigh monocytes 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.
Insights
Molecular imaging targeting myeloperoxidase (MPO) effectively detects early spinal cord inflammation after thoracic aortic ischemia-reperfusion (TAR) injury in mice. This approach shows promise for tracking inflammatory damage and neuronal loss in spinal cord injury models.
Area of Science:
- Biomedical Imaging
- Neuroscience
- Inflammation Research
Background:
- Spinal cord injury (SCI) following thoracic aortic ischemia-reperfusion (TAR) involves significant inflammation.
- Early detection of inflammation is crucial for understanding SCI pathogenesis and developing treatments.
- Myeloperoxidase (MPO) is a key enzyme in inflammatory processes, making it a potential imaging target.
Purpose of the Study:
- To evaluate noninvasive molecular imaging targeting MPO for early detection of inflammation in a mouse model of TAR-induced SCI.
- To assess the correlation between MPO activity, inflammatory markers, and neuronal loss.
Main Methods:
- Mice underwent TAR or sham surgery.
- Molecular imaging using Magnetic Resonance (MR) and Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) with MPO-targeted sensors was performed.
- Immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to quantify myeloid cells, neuronal loss, and cytokine levels (KC, IL-6).
Main Results:
- Molecular imaging revealed increased MPO activity and sensor retention in the injured spinal cord at 6 and 24 hours post-TAR.
- Significant myeloid cell infiltration and neuronal loss were observed, correlating inversely with MPO activity detected by imaging.
- Elevated levels of proinflammatory cytokines keratinocyte chemoattractant (KC) and interleukin 6 (IL-6) mirrored MPO activity.
Conclusions:
- Noninvasive molecular imaging targeting MPO can effectively identify and track early inflammatory damage in the spinal cord after TAR.
- MPO serves as a suitable imaging biomarker for assessing spinal cord inflammation and neuronal injury in this preclinical model.
- The findings support the potential of MPO-targeted imaging for future clinical applications in SCI.
