Resting-State Functional Magnetic Resonance Imaging of Interhemispheric Functional Connectivity in Experimental Traumatic Brain Injury.

Although resting-state functional magnetic resonance imaging (rsfMRI) has the potential to offer insights into changes in functional connectivity networks after traumatic brain injury (TBI), there are few studies that examine the effects of moderate TBI for monitoring functional recovery in experimental TBI, and thus the neural correlates of brain recovery from moderate TBI remain incompletely understood. Non-invasive rsfMRI was used to longitudinally investigate changes in interhemispheric functional connectivity (IFC) after a moderate TBI to the unilateral sensorimotor cortex in rats (n = 9) up to 14 days. Independent component analysis of the rsfMRI data was performed. Correlations of rsfMRI sensorimotor networks were made with changes in behavioral scores, lesion volume, and T2- and diffusion-weighted images across time. TBI animals showed less localized rsfMRI patterns in the sensorimotor network compared to sham (n = 6) and normal (n = 5) animals. rsfMRI clusters in the sensorimotor network showed less bilateral symmetry compared to sham and normal animals, indicative of IFC disruption. With time after injury, many of the rsfMRI patterns in the sensorimotor network showed more bilateral symmetry, indicative of IFC recovery. The disrupted IFC in the sensorimotor and subsequent partial recovery showed a positive correlation with changes in behavioral scores. Overall, rsfMRI detected widespread disruption and subsequent recovery of IFC within the sensorimotor networks post-TBI, which correlated with behavioral changes. Therefore, rsfMRI offers the means to probe functional brain reorganization and thus has the potential to serve as an imaging marker to longitudinally stage TBI and monitor for novel treatments.

The effects of perturbed cerebral blood flow and cerebrovascular reactivity on structural MRI and behavioral readouts in mild traumatic brain injury.

This study investigated the effects of perturbed cerebral blood flow (CBF) and cerebrovascular reactivity (CR) on relaxation time constant (T2), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and behavioral scores at 1 and 3 hours, 2, 7, and 14 days after traumatic brain injury (TBI) in rats. Open-skull TBI was induced over the left primary forelimb somatosensory cortex (N=8 and 3 sham). We found the abnormal areas of CBF and CR on days 0 and 2 were larger than those of the T2, ADC, and FA abnormalities. In the impact core, CBF was reduced on day 0, increased to 2.5 times of normal on day 2, and returned toward normal by day 14, whereas in the tissue surrounding the impact, hypoperfusion was observed on days 0 and 2. CR in the impact core was negative, most severe on day 2 but gradually returned toward normal. T2, ADC, and FA abnormalities in the impact core were detected on day 0, peaked on day 2, and pseudonormalized by day 14. Lesion volumes peaked on day 2 and were temporally correlated with forelimb asymmetry and foot-fault scores. This study quantified the effects of perturbed CBF and CR on structural magnetic resonance imaging and behavioral readouts.

Cerebral angiography, blood flow and vascular reactivity in progressive hypertension.

Chronic hypertension alters cerebral vascular morphology, cerebral blood flow (CBF), cerebrovascular reactivity, and increses susceptibility to neurological disorders. This study evaluated: i) the lumen diameters of major cerebral and downstream arteries using magnetic resonance angiography, ii) basal CBF, and iii) cerebrovascular reactivity to hypercapnia of multiple brain regions using arterial-spin-labeling technique in spontaneously hypertensive rats (SHR) at different stages. Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR, lumen diameter started to reduce, basal CBF, and hypercapnic CBF response were higher from elevated arterial blood pressure, but there was no evidence of stenosis, compared to age-matched WKY. In 20-week SHR, lumen diameter remained reduced, CBF returned toward normal from vasoconstriction, hypercapnic CBF response reversed and became smaller, but without apparent stenosis. In 40-week SHR, lumen diameter remained reduced and basal CBF further decreased, resulting in larger differences compared to WKY. There was significant stenosis in main supplying cerebral vessels. Hypercapnic CBF response further decreased, with some animals showing negative hypercapnic CBF responses in some brain regions, indicative of compromised cerebrovascular reserve. The territory with negative hypercapnia CBF responses corresponded with the severity of stenosis in arteries that supplied those territories. We also found enlargement of downstream vessels and formation of collateral vessels as compensatory responses to stenosis of upstream vessels. The middle cerebral and azygos arteries were amongst the most susceptible to hypertension-induced changes. Multimodal MRI provides clinically relevant data that might be useful to characterize disease pathogenesis, stage disease progression, and monitor treatment effects in hypertension.