Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury

Abstract

This study was designed to investigate whether functional and molecular MRI techniques are sensitive biomarkers for assessment of neuroinflammation and drug efficacy after traumatic brain injury (TBI) in rats. We subjected rats to a controlled cortical impact model and used behavioral tests, histology, and immunofluorescence to assess whether flavonoid pinocembrin provides cerebral protection and improves functional recovery. Most importantly, we used multiple noninvasive structural, functional, and molecular MRI techniques to examine whether the pinocembrin-related neuroprotection and attenuation of neuroinflammation can be detected in vivo. Significant increases in cerebral blood flow (CBF) and amide proton transfer-weighted (APTw) MRI signals were observed in the perilesional areas in untreated TBI rats at 3 days and could be attributed to increased glial response. In addition, increased apparent diffusion coefficient and decreased magnetization transfer ratio signals in untreated TBI rats over time were likely due to edema. Post-treatment with pinocembrin decreased microglial/macrophage activation at 3 days, consistent with the recovery of CBF and APTw MRI signals in regions of secondary injury. These findings suggest that pinocembrin provides cerebral protection for TBI and that multiple MRI signals, CBF and APTw in particular, are sensitive biomarkers for identification and assessment of neuroinflammation and drug efficacy in the TBI model.

Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia

“…All MRI experiments were conducted on a standard 4.7 T horizontal-bore animal imager (Bruker Biospin, Billerica, MA), and images were analyzed with the IDL program (Exelis Visual Information Solutions, Inc., Boulder, CO) (Wang et al, 2015c; Wang et al, 2017; Zhou et al, 2013). To assess BBB permeability changes, we acquired T1-weighted spin-echo images (T1WIs) in the coronal plane (7 slices) before and after gadolinium contrast agent administration (0.4 mmol/kg gadoteridol, Bracco Diagnostics, Princeton, NJ).…”

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

“…Notably, unlike many currently used advanced MRI techniques, APTw MRI can provide visual interpretation (not just statistical differences in image analysis) for these key TBI pathophysiological features. Subsequently, Wang et al further examined the treatment efficacy of pinocembrin, a natural antiinflammatory and neuroprotective compound. They found that, at 3 days post‐TBI, the APTw signals in the ipsilateral cortex and hippocampus increased significantly in the TBI group compared with the sham group, but significantly decreased in the TBI + pinocembrin group, compared with the TBI group.…”

Towards the complex dependence of MTRasym on T1w in amide proton transfer (APT) imaging

“…Amide proton transfer (APT) is an important application of CEST imaging, which detects the chemical exchange between backbone amide protons of proteins/peptides and water protons . In the last decade, APT has been applied to diagnose tumors, ischemic stroke, multiple sclerosis, and traumatic brain injury …”

“…14 In the last decade, APT has been applied to diagnose tumors, 5,[15][16][17][18] ischemic stroke, [19][20][21][22] multiple sclerosis, 23 and traumatic brain injury. 24,25 However, CEST is an indirect method to detect solute molecules or pH through measurements of water signals, and thus depends on multiple other tissue parameters, including direct water saturation (DS), semi-solid magnetization transfer (MT), and water longitudinal relaxation time (T 1w ).…”