Abstract
A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining 18F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague–Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by 18F-FDG PET, MRI, and histological evaluation at baseline, 1–3 h, 1 day, and 7 days post-injury in three separate cohorts. 18F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased 18F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1–3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood–brain barrier. Increased 18F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that 18F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.
Highlights
Blast-induced traumatic brain injury (TBI), the most common injury of modern warfare, has been receiving great interest worldwide recently (Benzinger et al, 2009)
18F-FDG uptake in the amygdala and somatosensory cortex gradually returned to baseline from 1 to 7 days post-injury in the mild TBI (mTBI) group, with a significant difference in somatosensory cortex by 1 day (+ 6.12%, p = 0.0429) compared with the sham group (Figures 2A,C,D). 18F-FDG uptake in the motor cortex increased in the mTBI group from 1 day (+ 3.60%, p = 0.0326) to 7 days post-injury (+ 3.41%, p = 0.0446) (Figures 2A,E)
Our current study reveals five main findings: (1) no visible brain injuries were observed on conventional T1- and T2-weighted imaging until 7 days following exposure to blast; (2) Ins, Glx, FIGURE 2 | Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) reveals both increased and decreased brain metabolism in multiple regions after blast-induced mTBI. (A) Representative axial 18F-FDG PET images in the brain from anterior to posterior of a sham and a blast rat on day 1 post-blast
Summary
Blast-induced traumatic brain injury (TBI), the most common injury of modern warfare, has been receiving great interest worldwide recently (Benzinger et al, 2009). Even though the acute symptoms of mTBI may be mild and transient, experimental and clinical studies have found metabolic, biochemical, and structural changes caused by mTBI. Mild TBI causes a complex pathophysiological cascade, including dramatic alterations in ionic homeostasis (Katayama et al, 1991), disruption of the blood–brain barrier (BBB) (Walls et al, 2016; Kuriakose et al, 2018), injury-induced neuroinflammation (Kokiko-Cochran and Godbout, 2018; Missault et al, 2019), and diffuse axonal injury (Ling et al, 2012; Venkatasubramanian et al, 2020). Majority of mTBI patients experience neurological dysfunction with no findings on conventional clinical imaging methods, such as structural magnetic resonance imaging (MRI) or computed tomography (CT) (Le and Gean, 2009). Due to the difficulty of imaging assessment on mTBI patients, especially in the acute or subacute phase, there needs more emphasis on the development of advanced imaging modalities, so that the therapeutic management of mTBI patients can be improved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
