Ashwal S, Babikian T, Gardner-Nichols J, Freier M-C, Tong KA, Holshouser BA. Susceptibility-weighted imaging and proton magnetic resonance spectroscopy in assessment of outcome after pediatric ...traumatic brain injury.
To assess the role of magnetic resonance imaging, specifically magnetic resonance spectroscopy (MRS) and susceptibility-weighted imaging (SWI), in the evaluation of children with traumatic brain injury (TBI).
Literature review and data from our recently published clinical studies.
Children with pediatric TBI who underwent SWI. SWI is a 3-dimensional high-resolution magnetic resonance imaging technique that is more sensitive in detecting hemorrhagic lesions seen with diffuse axonal injury (DAI) than conventional imaging. MRS acquires metabolite information that reflects neuronal integrity and function from multiple brain regions and offers early prognostic information regarding outcome.
Literature review.
Literature review and review of recently published data from our institution.
The data suggest that more sensitive imaging techniques that provide early evidence of injury and that are better predictors of outcome are needed to identify children at risk for such deficits. Specifically, the number and volume of hemorrhagic DAI lesions as well as changes in spectral metabolites such as reduced
N-acetylaspartate or elevations in choline-related compounds correlate with neurologic disability and impairments of global intelligence, memory, and attention.
Diffuse axonal injury (DAI) after traumatic brain injury (TBI) is important in patient assessment and prognosis, yet they are underestimated with conventional imaging techniques. We used MR ...spectroscopic imaging (MRSI) to detect DAI and determine whether metabolite ratios are accurate in predicting long-term outcomes and to examine regional differences in injury between children with TBI and control subjects.
Forty children with TBI underwent transverse proton MRSI through the level of the corpus callosum within 1-16 days after injury. T2-weighted, fluid-attenuated inversion recovery, and susceptibility-weighted MR imaging was used to identify voxels as normal-appearing or as nonhemorrhagic or hemorrhagic injury. Neurologic outcome was evaluated at 6-12 months after injury. Metabolite ratios for total (all voxels), normal-appearing, and hemorrhagic brain were compared and used in a logistic regression model to predict long-term outcome. Total and regional metabolite ratios were compared with control data.
A significant decrease in N-acetylaspartate (NAA)/creatine (Cr) and increase in choline (Cho)/Cr (evidence of DAI) was observed in normal-appearing (P < .05) and visibly injured (hemorrhagic) brain (P < .001) compared with controls. In normal-appearing brain NAA/Cr decreased more in patients with poor outcomes (1.32 +/- 0.54) than in those with good outcomes (1.61 +/- 0.50, P = .01) or control subjects (1.86 +/- 0.1, P = .00). In visibly injured brains, ratios were similarly altered in all patients. In predicting outcomes, ratios from normal-appearing and visibly-injured brain were 85% and 67% accurate, respectively.
MRSI can depict injury in brain that appears normal on imaging and is useful for predicting long-term outcomes.
Traumatic brain injury is among the most frequent pediatric neurologic disorders in the United States, affecting multiple aspects of neuropsychologic functioning. This study assessed the efficacy of ...susceptibility weighted imaging as a predictor of long-term neuropsychologic functioning after pediatric brain injury compared with magnetic resonance spectroscopic imaging. Susceptibility weighted imaging is a relatively new method that is considered superior to traditional magnetic resonance imaging sequences for detecting hemorrhagic diffuse axonal injury. In this study, imaging and spectroscopy were acquired 6 ± 4 days after injury. Measures of neuropsychologic functioning were administered to 18 children and adolescents 1–4 years post injury. Negative correlations between lesion number and volume with neuropsychologic functioning were demonstrated. Lesion volume explained over 32% of the variance in cognitive performance, explaining at least an additional 20% beyond injury severity and age at injury alone and 19% beyond magnetic resonance spectroscopic metabolite variables. Exploratory analyses resulted in notable trends, with lesions in deeper brain regions more strongly associated with poorer neuropsychologic performance. Improved detection of the extent of diffuse axonal injury following a brain injury will allow for a better understanding of its association with long-term outcome, which in turn can improve prognostic efficacy for effective treatment planning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We evaluated proton magnetic resonance spectroscopic imaging (MRSI) findings for children with traumatic brain injury attributable to nonaccidental trauma (NAT) early after injury, to determine ...whether brain metabolite changes predicted outcomes.
Proton MRSI (1.5 T) was performed (mean: 5 days after injury range: 1-30 days) through the level of the corpus callosum for 90 children with confirmed NAT. Regional N-acetylaspartate/total creatine, N-acetylaspartate/total choline, and choline/creatine ratios and the presence of lactate were measured. Data on long-term outcomes defined at > or =6 months were collected for 44 of 90 infants. We grouped patients into good (normal, mild disability, or moderate disability; n = 32) and poor (severe disability, vegetative state, or dead; n = 12) outcome groups.
We found that N-acetylaspartate/creatine and N-acetylaspartate/choline ratios (mean total, corpus callosum, and frontal white matter) were significantly decreased in patients with poor outcomes (P < .001). A logistic regression model using age, initial Glasgow Coma Scale score, presence of retinal hemorrhage, lactate on MRSI scans, and mean total N-acetylaspartate/creatine ratio predicted outcomes accurately in 100% of cases.
Reduced N-acetylaspartate levels (ie, neuronal loss/dysfunction) and elevated lactate levels (altered energy metabolism) correlated with poor neurologic outcomes for infants with NAT. Elevated lactate levels may reflect primary or secondary hypoxic-ischemic injury, which may occur with NAT. Our data suggest that MRSI performed early after injury can be used for long-term prognosis.
A new iron sensitive MR sequence (susceptibility weighted imaging - SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to ...study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n = 73) and cognitively normal participants (n = 33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of BMB were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p = 0.035) and stable MCI (p = 0.01). BMB were detected in 9 out of 26 (38%) MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants risk ratio = 2.06 (95% confidence interval 1.37-3.12). SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR-based biomarkers for neurodegenerative diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aim: Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor agonists including adrenocorticotropic hormone ...(ACTH) ameliorate inflammation and provide a novel therapeutic approach. We examined the effect of long-acting cosyntropin (CoSyn), a synthetic ACTH analog, on the early inflammatory response and functional outcome following experimental TBI. Methods: The controlled cortical impact model was used to induce TBI in mice. Mice were assigned to injury and treatment protocols resulting in four experimental groups including sham + saline, sham + CoSyn, TBI + saline and TBI + CoSyn. Treatment was administered subcutaneously 3 hrs post injury and daily injections were given for up to seven days post injury. Early inflammatory response was evaluated at three days post injury through evaluation of cytokine expression (IL1β and TNFα) and immune cell response. Quantification of immune cell response included cell counts of microglia/macrophages (Iba1+ cells) and neutrophils (MPO+ cells) in cortex and hippocampus. Behavioral testing (n=10-14 animals/group) included open field and novel object recognition during the first week following injury and Morris water maze at 10-15 days post injury. Results: Immune cell quantification showed decreased accumulation of Iba1+ cells in the perilesional cortex and CA1 region of the hippocampus for CoSyn-treated TBI animals compared to saline-treated. Reduced numbers of MPO+ cells were also found in the perilesional cortex and hippocampus in CoSyn treated TBI mice compared to their saline treated counterparts. Furthermore, CoSyn treatment reduced IL1β expression in the cortex of TBI mice. Behavioral testing showed a treatment effect of CoSyn for novel object recognition with CoSyn increasing the discrimination ratio in both TBI and Sham groups, indicating increased memory performance. CoSyn also decreased latency to find platform during the early training period of the Morris water maze when comparing CoSyn to saline-treated TBI mice suggesting moderate improvements in spatial memory following CoSyn treatment. Conclusion: Reduced microglia/macrophage accumulation and neutrophil infiltration in conjunction with moderate improvements in spatial learning in our CoSyn treated TBI mice suggests a beneficial anti-inflammatory effect of CoSyn following TBI.
Proton magnetic resonance spectroscopy (MRS) is being used to evaluate individuals with acute traumatic brain injury and several studies have shown that changes in certain brain metabolites ...(N-acetylaspartate, choline) are associated with poor neurologic outcomes. The majority of previous MRS studies have been obtained relatively late after injury and none have examined the role of glutamate/ glutamine (Glx). We conducted a prospective MRS study of 42 severely injured adults to measure quantitative metabolite changes early (7 days) after injury in normal appearing brain. We used these findings to predict long-term neurologic outcome and to determine if MRS data alone or in combination with clinical outcome variables provided better prediction of long-term outcomes. We found that glutamate/glutamine (Glx) and choline (Cho) were significantly elevated in occipital gray and parietal white matter early after injury in patients with poor long-term (6-12-month) outcomes. Glx and Cho ratios predicted long-term outcome with 94% accuracy and when combined with the motor Glasgow Coma Scale score provided the highest predictive accuracy (97%). Somatosensory evoked potentials were not as accurate as MRS data in predicting outcome. Elevated Glx and Cho are more sensitive indicators of injury and predictors of poor outcome when spectroscopy is done early after injury. This may be a reflection of early excitotoxic injury (i.e., elevated Glx) and of injury associated with membrane disruption (i.e., increased Cho) secondary to diffuse axonal injury.
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