Volumetric brain magnetic resonance imaging analysis in children with obstructive sleep apnea.

OBJECTIVES: Pediatric Obstructive Sleep Apnea (OSA) is associated with neurocognitive deficits. Cerebral structural alterations in the frontal cortex, cerebellum, and hippocampus have been reported in adult OSA patients. These brain areas are important for executive functioning, motor regulation of breathing, and memory function, respectively. Corresponding evidence comparing cerebral structures in pediatric OSA patients is limited. The objective of this study is to investigate MRI differences in cortical thickness and cortical volume in children with and without OSA. STUDY DESIGN: Prospective, single institutional case-control study. METHODS: Forty-five children were recruited at a pediatric tertiary care center (27 with OSA; mean age 9.9 ± 1.9 years, and 18 controls; mean age 10.5 ± 1.0 years). The OSA group underwent magnetic resonance imaging (MRI), polysomnography (PSG) and completed the Pediatric Daytime Sleepiness Scale (PDSS) and the Child's Sleep Habits Questionnaire (CSHQ). High-resolution T1-weighted MRI was utilized to examine cortical thickness and gray and white matter volume in children with OSA compared to a healthy group of demographically-comparable children without OSA selected from a pre-existing MRI dataset. RESULTS: Children with OSA showed multiple regions of cortical thinning primarily in the left hemisphere. Reduced gray matter (GM) volume was noted in the OSA group in multiple frontal regions of the left hemisphere (superior frontal, rostral medial frontal, and caudal medial frontal regions). Reduced white matter (WM) volume in both the left and right hemisphere was observed in regions of the frontal, parietal, and occipital lobes in children with OSA. CONCLUSION: This study noted differences in cortical thickness and GM and WM regional brain volumes in children with OSA. These findings are consistent with other pediatric studies, which also report differences between healthy children and those with OSA. We found that the severity of OSA does not correlate with the extent of MRI alterations.

Orthopedic Injured versus Uninjured Comparison Groups for Neuroimaging Research in Mild Traumatic Brain Injury.

To address controversy surrounding the most appropriate comparison group for mild traumatic brain injury (mTBI) research, mTBI patients 12-30 years of age were compared with an extracranial orthopedic injury (OI) patient group and an uninjured, typically developing (TD) participant group with comparable demographic backgrounds. Injured participants underwent subacute (within 96 h) and late (3 months) diffusion tensor imaging (DTI); TD controls underwent DTI once. Group differences in fractional anisotropy (FA) and mean diffusivity (MD) of commonly studied white matter tracts were assessed. For FA, subacute group differences occurred in the bilateral inferior frontal occipital fasciculus (IFOF) and right inferior longitudinal fasciculus (ILF), and for MD, differences were found in the total corpus callosum, right uncinate fasciculus, IFOF, ILF, and bilateral cingulum bundle (CB). In these analyses, differences (lower FA and higher MD) were generally observed between the mTBI and TD groups but not between the mTBI and OI groups. After a 3 month interval, groups significantly differed in left IFOF FA and in right IFOF and CB MD; the TD group had significantly higher FA and lower MD than both injury groups, which did not differ. There was one exception to this pattern, in which the OI group demonstrated significantly lower FA in the left ILF than the TD group, although neither group differed from the mTBI group. The mTBI and OI groups had generally similar longitudinal results. Findings suggest that different conclusions about group-level DTI analyses could be drawn, depending on the selected comparison group, highlighting the need for additional research in this area. Where possible, mTBI studies may benefit from the inclusion of both OI and TD controls.

Chronic Effects of Boxing: Diffusion Tensor Imaging and Cognitive Findings.

We used magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to evaluate the effects of boxing on brain structure and cognition in 10 boxers (8 retired, 2 active; mean age = 45.7 years; standard deviation [SD] = 9.71) and 9 participants (mean age = 43.44; SD = 9.11) in noncombative sports. Evans Index (maximum width of the anterior horns of the lateral ventricles/maximal width of the internal diameter of the skull) was significantly larger in the boxers (F = 4.52; p = 0.050; Cohen's f = 0.531). Word list recall was impaired in the boxers (F(1,14) = 10.70; p = 0.006; f = 0.84), whereas implicit memory measured by faster reaction time (RT) to a repeating sequence of numbers than to a random sequence was preserved (t = 2.52; p < 0.04). Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) measured by tractography did not significantly differ between groups. However, DTI metrics were significantly correlated with declarative memory (e.g., left ventral striatum ADC with delayed recall, r = -0.74; p = 0.02) and with RT to the repeating number sequence (r = 0.70; p = 0.04) in the boxers. Years of boxing had the most consistent, negative correlations with FA, ranging from -0.65 for the right ventral striatum to -0.92 for the right cerebral peduncle. Years of boxing was negatively related to the number of words consistently recalled over trials (r = -0.74; p = 0.02), delayed recall (r = -0.83; p = 0.003), and serial RT (r = 0.66; p = 0.05). We conclude that microstructural integrity of white matter tracts is related to declarative memory and response speed in boxers and to the extent of boxing exposure. Implications for chronic traumatic encephalopathy are discussed.

Centrum semiovale and corpus callosum integrity in relation to information processing speed in patients with severe traumatic brain injury.

OBJECTIVES: This study investigated white matter alterations in the corpus callosum (CC) and centrum semiovale (CSO), using diffusion tensor imaging and magnetization transfer imaging, in participants with severe traumatic brain injury (TBI) and related these changes to processing speed measures. PARTICIPANTS AND METHODS: Fourteen adult participants with severe TBI underwent neuroimaging and assessment, using the Symbol Digit Modalities Test and Trail-Making Test, Part B, at approximately 6 months postinjury. Thirteen demographically similar, neurologically intact adults were imaged for comparison. RESULTS: The TBI group demonstrated lower fractional anisotropy (FA) for the right CSO and higher apparent diffusion coefficient (ADC) for the CSO bilaterally than the control group. Lower FA and higher ADC were noted in all CC regions. Magnetization transfer imaging revealed smaller magnetization transfer ratios (MTRs) in the right and left CSO and CC genu and splenium. Written Symbol Digit Modalities Test performance was related to right CSO FA, bilateral CSO ADC, CC FA, and right CSO MTR, whereas oral Symbol Digit Modalities Test was related to right CSO FA, ADC, and MTR. Trail-Making Test, Part B, was related to right CSO FA and MTR. CONCLUSIONS: Advanced neuroimaging modalities such as diffusion tensor imaging and magnetization transfer imaging demonstrate significant alterations in white matter, which are related to processing speed. These techniques may be useful in quantifying the extent of injury even in normal appearing white matter after TBI.

Serial measurement of memory and diffusion tensor imaging changes within the first week following uncomplicated mild traumatic brain injury.

Patients (n = 8) with uncomplicated mild traumatic brain injury (mTBI) underwent serial assessments (4) with diffusion tensor imaging (DTI) and neuropsychological testing within the first 8 days post-injury. Using a multi-case study design, we examined changes in brain parenchyma (via DTI-derived fractional anisotropy [FA], apparent diffusion coefficient [ADC], axial diffusivity [AD] and radial diffusivity [RD] in the left cingulum bundle) and in memory performance (via Hopkins Verbal Learning Test-Revised). Qualitative inspection of the results indicated that memory performance was transiently affected in most participants over the course of the week, with performance most negatively impacted on the second assessment (days 3-4 or 97-144 h post-injury), and then returning to within normal limits by 8 days post-injury. Alternatively, FA and other DTI metrics showed a more complex pattern, with the trajectory of some participants changing more prominently than others. For example, FA transiently increased in some participants over the study period, but the pattern was heterogeneous. Memory performance appeared to mirror changes in FA in certain cases, supporting a pathophysiological basis to memory impairment following mTBI. However, the pattern and the degree of symmetry between FA and memory performance was complex and did not always correspond. Serial imaging over the semi-acute recovery period may be important in reconciling conflicting findings in mTBI utilizing memory and/or DTI. Serial use of imaging modalities including DTI may aid understanding of underlying pathophysiological changes in the semi-acute post-injury period. Should a consistent pattern emerge that allows identification of patients at-risk for acute and/or persistent symptoms, such knowledge could guide development of therapeutic targets in mTBI and in understanding the most effective administration time window for these agents.

Diffusion tensor imaging in moderate-to-severe pediatric traumatic brain injury: changes within an 18 month post-injury interval.

Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet little is known regarding the pattern of TBI-related microstructural change and its impact on subsequent development. Diffusion tensor imaging (DTI) was used to examine between-group differences at two time points (planned intervals of 3 months and 18 months post-injury) and within-group longitudinal change in a group of children and adolescents aged 7-17 years with moderate-to-severe TBI (n = 20) and a comparison group of children with orthopedic injury (OI) (n = 21). In the 3- and 18-month cross-sectional analyses, tract-based spatial statistics (TBSS) generally revealed decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI group in regions of frontal, temporal, parietal, and occipital white matter as well as several deep subcortical structures, though areas of FA decrease were more prominent at the 3-month assessment, and areas of ADC increase were more prominent at the 18 month assessment, particularly in the frontal regions. In terms of the within-group changes over time, the OI group demonstrated primarily diffuse increases in FA over time, consistent with previous findings of DTI-measured white matter developmental change. The TBI group demonstrated primarily regions of FA decrease and ADC increase over time, consistent with presumed continued degenerative change, though regions of ADC decrease were also appreciated. These results suggest that TBI-related microstructural changes are dynamic in children and continue until at least 18 months post-injury. Understanding the course of these changes in DTI metrics may be important in TBI for facilitating advances in management and intervention.

Diffusion tensor imaging of incentive effects in prospective memory after pediatric traumatic brain injury.

Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n=37) or moderate-to-severe TBI (n=40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p=0.003), left orbitofrontal WM (p<0.02), and left (p<0.02) and right (p<0.008) uncinate fasciculi significantly predicted EB-PM performance in the high motivation condition. We infer that the cingulum bundles, orbitofrontal WM, and uncinate fasciculi are important WM structures mediating motivation-based EB-PM responses following moderate-to-severe TBI in children.

Longitudinal changes in the corpus callosum following pediatric traumatic brain injury.

BACKGROUND: Atrophy of the corpus callosum (CC) is a documented consequence of moderate-to-severe traumatic brain injury (TBI), which has been expressed as volume loss using quantitative magnetic resonance imaging (MRI). Other advanced imaging modalities such as diffusion tensor imaging (DTI) have also detected white matter microstructural alteration following TBI in the CC. The manner and degree to which macrostructural changes such as volume and microstructural changes develop over time following pediatric TBI, and their relation to a measure of processing speed is the focus of this longitudinal investigation. As such, DTI and volumetric changes in the CC in participants with TBI and a comparison group at approximately 3 and 18 months after injury as well as their relation to processing speed were determined. METHODS: Forty-eight children and adolescents aged 7-17 years who sustained either complicated mild or moderate-to-severe TBI (n = 23) or orthopedic injury (OI; n = 25) were studied. The participants underwent brain MRI and were administered the Eriksen flanker task at both time points. RESULTS: At 3 months after injury, there were significant group differences in DTI metrics in the total CC and its subregions (genu/anterior, body/central and splenium/posterior), with the TBI group demonstrating significantly lower fractional anisotropy (FA) and a higher apparent diffusion coefficient (ADC) in comparison to the OI group. These group differences were also present at 18 months after injury in all CC subregions, with lower FA and a higher ADC in the TBI group. In terms of longitudinal changes in DTI, despite the group difference in mean FA, both groups generally demonstrated a modest increase in FA over time though this increase was only significant in the splenium/posterior subregion. Interestingly, the TBI group also generally demonstrated ADC increases from 3 to 18 months though the OI group demonstrated ADC decreases over time. Volumetrically, the group differences at 3 months were marginal for the midanterior and body/central subregions and total CC. However, by 18 months, the TBI group demonstrated a significantly decreased volume in all subregions except the splenium/posterior area relative to the OI group. Unlike the OI group, which showed a significant volume increase in subregions of the CC over time, the TBI group demonstrated a significant and consistent volume decrease. Performance on a measure of processing speed did not differentiate the groups at either visit, and only the OI group showed significantly improved performance over time. Processing speed was related to FA in the splenium/posterior and total CC only in the TBI group on both occasions, with a stronger relation at 18 months. CONCLUSION: In response to TBI, macrostructural volume loss in the CC occurred over time; yet, at the microstructural level, DTI demonstrated both indicators of continued maturation and development even in the damaged CC, as well as evidence of potential degenerative change. Unlike volumetrics, which likely reflects the degree of overall neuronal loss and axonal damage, DTI may reflect some aspects of postinjury maturation and adaptation in white matter following TBI. Multimodality imaging studies may be important to further understand the long-term consequences of pediatric TBI.

The temporal stem in traumatic brain injury: preliminary findings.

The temporal stem (TS) of the temporal lobe is a major white matter (WM) region containing several major pathways that connect the temporal lobe with the rest of the brain. Because of its location, it may be particularly vulnerable to shear-strain effects resulting from traumatic brain injury (TBI). A case vignette is presented in a patient with severe brain injury and focal TS pathology. Also, 12 severe TBI subjects unselected for TS pathology were compared to demographically matched, neurologically-intact controls using diffusion tensor imaging (DTI) to examine white matter tracts associated with the TS, including the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus (AF), cingulum bundle (CB) and the uncinate fasciculus (UF). For each tract, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and compared between the two groups and also examined in relationship to memory performance in the TBI subjects. Significant FA and ADC differences were observed in all tracts in the TBI patients compared to controls, with several relationships with memory outcome noted in the IFOF, ILF and AF. Based on these preliminary findings, the potential role of TBI-induced WM disconnection involving the TS is discussed as well as the relationship of TS damage to neurobehavioral outcome. The need for future studies specifically examining the role of TS injury in TBI is emphasized.

Diffusion tensor imaging of the cingulum bundle in children after traumatic brain injury.

Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.

Diffusion tensor imaging analysis of frontal lobes in pediatric traumatic brain injury.

This study examined the use of diffusion tensor imaging in detecting white matter changes in the frontal lobes following pediatric traumatic brain injury. A total of 46 children (ages 8-16 years) with moderate to severe traumatic brain injury and 47 children with orthopedic injury underwent 1.5 Tesla magnetic resonance imaging (MRI) at 3 months postinjury. Conventional MRI studies were obtained along with diffusion tensor imaging. Diffusion tensor imaging metrics, including fractional anisotropy, apparent diffusion coefficient, and radial diffusivity, were compared between the groups. Significant group differences were identified, implicating frontal white matter alterations in the injury group that were predictive of later Glasgow Outcome Scale ratings; however, focal lesions were not related to the Glasgow Outcome Scale ratings. Injury severity was also significantly associated with diffusion tensor imaging metrics. Diffusion tensor imaging holds great promise as an index of white matter integrity in traumatic brain injury and as a potential biomarker reflective of outcome.

Evaluating the relationship between memory functioning and cingulum bundles in acute mild traumatic brain injury using diffusion tensor imaging.

Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p < 0.001). Despite the marginal significance of the group difference in fractional anisotropy (FA), the effect size between groups was moderate (d = 0.66). Cognitively, healthy controls performed better than the TBI group on immediate and delayed recall; however, the difference did not reach statistical significance. In the mTBI group, FA of the left cingulum bundle was significantly correlated with 30-min delayed recall (r = -0.56, p = 0.05). A marginally significant correlation was found between ADC of the left cingulum bundle and the total words of immediate recall (r = 0.59, p = 0.07). No significant correlation was found between DTI metrics and memory functioning for the control group. These preliminary findings indicate that cingulate injury likely contributes to the cognitive sequelae seen during the early phase post-mTBI.