Changes in Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy in a Direct Cranial Blast Traumatic Brain Injury (dc-bTBI) Model

Abstract

Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1–14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14–19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS.

Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study

“…Another study using a blast TBI model also revealed higher MK values at 7, 14, and 28 days after TBI. 34 Our study also found higher MD values only at 3 days after TBI, and higher FA values at 3 and 28 days after TBI. Our study indicated that MK is more sensitive to detect microstructural changes in the hippocampus.…”

Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids

“…It has been indicated that both compounds, besides various still debated biological functions [51][52][53][54][55], play a determining contribution in controlling cerebral osmolarity [52,55,56]. Even though some studies showed a decrease in Tau after TBI [57][58][59], our results are in line with those reported by others [60,61] and are logically connected to dysfunctional NAA homeostasis following sTBI and to a precise role of osmolite regulator performed by cerebral Tau. It is also possible that the increase in Tau is finalized to counteract Glu excitotoxic effects since it has been reported that Tau can directly interact with the NMDA receptor subtype decreasing the binding of Glu [62].…”

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

“…Notably, the alteration in radial anisotropy displayed the largest effect size and were directly correlated with histological measures of axonal damage (Li et al, 2013 ; Tu et al, 2016 ; also in rat models). FA maps have demonstrated substantial microstructural abnormalities also in case of experimental blast injury in mouse (Rubovitch et al, 2011 ; Hutchinson et al, 2018 ; Venkatasubramanian et al, 2020 ; Weiss et al, 2020 ) as well as in rat models (Budde et al, 2013 ; Begonia et al, 2014 ; Kamnaksh et al, 2014 ; Zhuo et al, 2015 ; Tang et al, 2017 ; Badea et al, 2018 ; Missault et al, 2019 ; Mohamed et al, 2020 ; San Martín Molina et al, 2020 ). DTI appeared sensitive enough to detect changes even in mild TBI models (Hylin et al, 2013 ; Takeuchi et al, 2013 ; Long et al, 2015 ; Li et al, 2016 ; Herrera et al, 2017 ; Kikinis et al, 2017 ; Wendel et al, 2018 ; Hoogenboom et al, 2019 ) and in distant locations within the brain up to 1 year after injury (Pischiutta et al, 2018 ).…”

“…Recently, DKI has been added to the MRI toolset for TBI investigation and has been able to detect changes in injured cortex in a CCI model of brain injury as soon as 5 h (Hansen et al, 2017 ; Soni et al, 2019 ). Although the DKI approach is in principle more sensitive to complex microstructural changes occurring upon trauma in mice and rats (Zhuo et al, 2015 ; Wang et al, 2018 ; Braeckman et al, 2019 ; Yu et al, 2019 ), its role is not established and remains object of investigation.…”