Distinct MRI pattern in lesional and perilesional area after traumatic brain injury in rat — 11 months follow-up

To understand the dynamics of progressive brain damage after lateral fluid-percussion induced traumatic brain injury (TBI) in rat, which is the most widely used animal model of closed head TBI in humans, MRI follow-up of 11 months was performed. The evolution of tissue damage was quantified using MRI contrast parameters T 2 , T 1ρ , diffusion (D av ), and tissue atrophy in the focal cortical lesion and adjacent areas: the perifocal and contralateral cortex, and the ipsilateral and contralateral hippocampus. In the primary cortical lesion area, which undergoes remarkable irreversible pathologic changes, MRI alterations start at 3 h postinjury and continue to progress for up to 6 months. In more mildly affected perifocal and hippocampal regions, the robust alterations in T 2 , T 1ρ , and D av at 3 h to 3 d post-injury normalize within the next 9-23 d, and thereafter, progressively increase for several weeks. The severity of damage in the perifocal and hippocampal areas 23 d post-injury appeared independent of the focal lesion volume. Magnetic resonance spectroscopy (MRS) performed at 5 and 10 months post-injury detected metabolic alterations in the ipsilateral hippocampus, suggesting ongoing neurodegeneration and inflammation. Our data show that TBI induced by lateral fluid-percussion injury triggers long-lasting alterations with region-dependent temporal profiles. Importantly, the temporal pattern in MRI parameters during the first 23 d post-injury can indicate the regions that will develop secondary damage. This information is valuable for targeting and timing interventions in studies aiming at alleviating or reversing the molecular and/or cellular cascades causing the delayed injury

Quantitative assessment of water pools by T 1 rho and T 2 rho MRI in acute cerebral ischemia of the rat

The rotating frame longitudinal relaxation MRI contrast, T(1ρ), obtained with on-resonance continuous wave (CW) spin-lock field is a sensitive indicator of tissue changes associated with hyperacute stroke. Here, the rotating frame relaxation concept was extended by acquiring both T(1ρ) and transverse rotating frame (T(2ρ)) MRI data using both CW and adiabatic hyperbolic secant (HSn, n = 1, 4, or 8) pulses in a rat stroke model of middle cerebral artery occlusion (MCAo). The results demonstrate differences in the sensitivity of spin-lock T(1ρ) and T(2ρ) MRI to detect hyperacute ischemia. The most sensitive techniques were CW-T(1ρ) and T(1ρ) using HS4 or HS8 pulses. Fitting a two-pool exchange model to the T(1ρ) and T(2ρ) MRI data acquired from the infarcting brain indicated time-dependent increase in free water fraction, decrease in the correlation time of water fraction associated with macromolecules and increase in the exchange correlation time. These findings are consistent with known pathology in acute stroke, including vasogenic edema, destructive processes and tissue acidification. Our results demonstrate that the sensitivity of the spin-lock MRI contrast in vivo can be modified using different spin-lock preparation blocks, and that physico-chemical models of the rotating frame relaxation may provide insight into progression of ischemia in vivo

Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI) in Permanent Focal Cerebral Ischemia in Rat

Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT) parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI), were quantified together with conventional relaxation parameters (T1, T2 and T1ρ) and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1) Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2) RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3) MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4) ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke

Spontaneous BOLD waves – A novel hemodynamic activity in Sprague-Dawley rat brain detected by functional magnetic resonance imaging

We report spontaneous hemodynamic activity termed “Spontaneous BOLD Waves” (SBWs) detected by BOLD fMRI in Sprague-Dawley rats under medetomidine anesthesia. These SBWs, which lasted several minutes, were observed in cortex, thalamus and hippocampus. The SBWs’ correlates were undetectable in electrophysiological recordings, suggesting an exclusive gliovascular phenomenon dissociated from neuronal activity. SBWs were insensitive to the NMDA receptors antagonist MK-801 but were inhibited by the α1-adrenoceptor blocker prazosin. Since medetomidine is a potent agonist of α2 adrenoceptors, we suggested that imbalance in α1/α2 receptor-mediated signalling pathways alter the vascular reactivity leading to SBWs. The frequency of SBWs increased with intensity of mechanical lung ventilation despite the stable pH levels. In summary, we present a novel type of propagating vascular brain activity without easily detectable underlying neuronal activity, which can be utilized to study the mechanisms of vascular reactivity in functional and pharmacological MRI and has practical implications for designing fMRI experiments in anesthetized animals. </jats:p

The measured relaxation rates in the sham-operated animals.

<p>The figures presented are mean values of areas in both hemispheres and the six time points. No systematic variation across the hemispheres, between the time points or between the animals was observed. These values agree closely with the relaxation data measured in the contralateral hemispheres of the stroke animals as well.</p