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.