Investigation of Asleep versus Awake Motor Mapping in Resective Brain Surgery.

OBJECTIVE: To develop an asleep motor mapping paradigm for accurate detection of the corticospinal tract during glioma surgery and compare outcomes with awake patients undergoing glioma resection. METHODS: A consecutive cohort of adult patients undergoing craniotomy for suspected diffuse glioma with tumor in a perirolandic location who had awake or asleep cortical and subcortical motor mapping with positive areas of motor stimulation were assessed for postoperative extent of resection (EOR), permanent neurological deficit, and proximity of stimulation to diffusion tensor imaging-based corticospinal tract depiction on preoperative magnetic resonance imaging. Outcome data were compared between asleep and awake groups. RESULTS: In the asleep group, all 16 patients had improved or no change in motor function at last follow-up (minimum 3 months of follow-up). In the awake group, all 23 patients had improved function or no change at last follow-up. EOR was greater in the asleep group (mean [SD] EOR 88.71% [17.56%]) versus the awake group (mean [SD] EOR 80.62% [24.44%]), although this difference was not statistically significant (P = 0.3802). Linear regression comparing distance from stimulation to corticospinal tract in asleep (n = 14) and awake (n = 4) patients was r = -0.3759, R2 = 0.1413, P = 0.1853, and 95% confidence interval = -0.4453 to 0.09611 and r = 0.7326, R2 = 0.5367, P = 0.2674, and 95% confidence interval = -7.042 to 14.75, respectively. CONCLUSION: In this small patient series, asleep motor mapping using commonly available motor evoked potential hardware appears to be safe and efficacious in regard to EOR and functional outcomes.

General anaesthesia during infancy reduces white matter micro-organisation in developing rhesus monkeys.

BACKGROUND: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. METHODS: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. RESULTS: Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. CONCLUSIONS: Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.

The diffusion-tensor imaging reveals alterations in water diffusion parameters in acute pediatric concussion.

Wide-spread visualization methods which are computed tomography (CT) and magnetic resonance imaging (MRI) are not sensitive to mild traumatic brain injury (mTBI). However, mTBI may cause changes of cerebral microstructure that could be found using diffusion-tensor imaging. The aim of this study is to reveal the impact of acute mTBI (no more than 3 days after trauma) on diffusion parameters in corpus callosum, corticospinal tract, and thalamus in children (aged 14-18). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were analyzed. Significant increase in FA and decrease in ADC were observed in thalamus. The trend to an increase in FA is observed in corpus callosum.

White matter changes from mild cognitive impairment to Alzheimer's disease: a meta-analysis.

Previous diffusion tensor imaging (DTI) studies have reported that both mild cognitive impairment (MCI) and Alzheimer's disease (AD) revealed microstructural changes [fractional anisotropy (FA)]. However, these results were not conclusive. The purpose of this meta-analysis was to identify the consistent FA alterations and the differences between MCI and AD. Case-control studies investigating MCI and AD using FA were searched in the online databases. The quantitative FA value of cognition-related brain regions was extracted and the standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using fixed or random effect models. Twenty six studies with a total of 1,021 patients were included in this meta-analysis. Significantly decreased FA in patients with AD were identified in the left frontal lobe, corpus callosum (CC), fornix, hippocampus (HP), cingulate gyrus (CG), cingulate bundle (CB), uncinate fasciculus (UF), superior longitudinal fasciculus(SLF), the inferior fronto-occipital fascicles (IFOF), and the inferior longitudinal fasciculus(ILF) relative to MCI in this meta-analysis. This study provides objective and quantitative evidence that AD is associated with FA alteration within left frontal lobe, CC, FX, HP, CG, CB, and UF may suggest the key regions of the process from MCI to AD.

Splenium tracts of the corpus callosum degrade in old age.

It is well established that the posterior region of the corpus callosum, known as the splenium, is relatively preserved during the course of normal ageing. However, the effect of age on its distinct interhemispheric tract bundles that project to bilateral occipital, parietal and temporal areas of the cortex, is largely unknown. In the present study, diffusion tensor imaging was used to directly examine the integrity of these distinct segregations and their diffusion metrics were compared between groups of young adults (n = 20, mean age = 30.75) and older adults (n = 19, mean age = 80.21). Results revealed that while occipital tracts were preserved in older adults, parietal and temporal segments were particularly impaired. These findings are the first to indicate the existence of selective alterations in the posterior region of the corpus callosum in older age.

Sex Differences in Anatomical Rich-Club and Structural-Functional Coupling in the Human Brain Network.

Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non-rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.

Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

White Matter Integrity in Tanzanian Children With Sickle Cell Anemia: A Diffusion Tensor Imaging Study.

Background and Purpose- Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods- Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results- Compared with SCI- patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb (P<0.005). Compared with VSC- patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions (P<0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. Conclusions- SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.

Tractography and the connectome in neurosurgical treatment of gliomas: the premise, the progress, and the potential.

The ability of diffusion tensor MRI to detect the preferential diffusion of water in cerebral white matter tracts enables neurosurgeons to noninvasively visualize the relationship of lesions to functional neural pathways. Although viewed as a research tool in its infancy, diffusion tractography has evolved into a neurosurgical tool with applications in glioma surgery that are enhanced by evolutions in crossing fiber visualization, edema correction, and automated tract identification. In this paper the current literature supporting the use of tractography in brain tumor surgery is summarized, highlighting important clinical studies on the application of diffusion tensor imaging (DTI) for preoperative planning of glioma resection, and risk assessment to analyze postoperative outcomes. The key methods of tractography in current practice and crucial white matter fiber bundles are summarized. After a review of the physical basis of DTI and post-DTI tractography, the authors discuss the methodologies with which to adapt DT image processing for surgical planning, as well as the potential of connectomic imaging to facilitate a network approach to oncofunctional optimization in glioma surgery.

Comparison of Acute Diffusion Tensor Imaging and Conventional Magnetic Resonance Parameters in Predicting Long-Term Outcome after Blunt Cervical Spinal Cord Injury.

This prospective longitudinal study compares the ability of conventional and diffusion tensor imaging (DTI) parameters made at the cervical spinal cord injury (CSCI) site to predict long-term neurological and functional outcomes. Twenty patients with CSCI, with follow-up at 6 or 12 months, and 15 control volunteers were included. Conventional magnetic resonance imaging (MRI) and DTI parameters were measured on admission and follow-up studies. Stepwise regression analysis was performed to find relevant parameters (normalized DTI values, conventional MRI measurements, hemorrhagic contusion [HC] or non-HC [NHC]) that correlated with three primary outcome measures: patient International Standards for Neurological Classification of Spinal Cord Injury total motor score (ISNCSCI-TMS), ability to walk, and expected recovery of upper limb motor scores (ER-ULMS) at 6 or 12 months. Univariate analysis showed HC (p < 0.0001 to 0.0098), lesion length on follow-up MRI (p < 0.0001 to 0.019), mean diffusivity (p = 0.01 to 0.045), and axial diffusivity (p = 0.004 to 0.023) predicted all three primary outcomes. Conspicuity of HC was significantly better on axial susceptibility-weighted imaging (SWI) compared with T2* images (p = 0.0009). A negative correlation existed between HC volumes on sagittal SWI images and follow-up ISNCSCI-TMS ( p = 0.02). The regression model identified NHC as the best predictor of the ability to walk (sensitivity = 88.9%; specificity = 100%; positive predictive value = 100%; negative predictive value = 91%; p < 0.0001) and lesion length on follow-up MRI as the best predictor of ER-ULMS (ß coefficient = 0.12, standard error [SE] = 0.07; R2 = 0.64; p = 0.0002). Finally, NHC (ß coefficient = 24.2, SE = 3.7; p < 0.0001) and lesion length on initial MRI (ß coefficient = 0.78, SE = 0.2; p = 0.002) were the best predictors of ISNCSCI-TMS (R2 = 0.83; p < 0.0001). Our study demonstrates HC and follow-up lesion length are potential neuroimaging biomarkers in predicting long-term neurological and functional outcome following blunt CSCI.

Differential White Matter Maturation from Birth to 8 Years of Age.

Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0-8 years and 31 children with autistic spectrum disorder (ASD) aged 2-7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0-8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0-8 years provide reference standards for biomarker detection of neuropsychiatric disorders.

Examining Microstructural White Matter Differences between Children with Typical and Those with Delayed Recovery Two Weeks Post-Concussion.

Delayed recovery from concussion can dramatically affect a child's social, emotional, and educational development, yet little is known about what causes some children to recover faster than others. The contribution of white matter disruption in children with delayed recovery has been hypothesized, but findings are limited by methodological issues such as: small heterogeneous samples, bias toward children with delayed recovery, and inconsistencies in timing of brain imaging, both within and between studies. The aim of the present study was to assess diffusion neuroimaging correlates of delayed recovery post-concussion in children. A prospective, longitudinal, observational cohort study was conducted at a statewide tertiary pediatric hospital. Forty-three children who presented to the emergency department (ED) with concussion (defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport) underwent magnetic resonance imaging (MRI) at a 2 weeks post-injury and were classified as either normally recovering (n = 26) or delayed recovering (n = 17). Diffusion imaging comparison using voxelwise tract-based spatial statistics (TBSS) analysis found no difference between the groups in fractional anisotropy, axial diffusion, radial diffusion, or mean diffusivity metrics (p > 0.05 threshold-free cluster enhancement [TFCE] corrected). Post-hoc tract-based Bayesian analysis found evidence for the null in 11 unique white matter tracts (Bayes factor >3). These findings indicate that delayed recovery from post-concussive symptoms in children is unlikely to be caused by white matter microstructural damage.

Changes in diffusion tensor imaging indices of the lumbosacral enlargement correlate with cervical spinal cord changes and clinical assessment in patients with cervical spondylotic myelopathy.

OBJECTIVES: We examined whether changes in diffusion tensor imaging (DTI) indices of the lumbosacral enlargement are similar to those at the cervical level, and correlate with clinical assessments in patients with cervical spondylotic myelopathy (CSM). PATIENTS AND METHODS: Patients with CSM and healthy volunteers (40-42/group) received DTI scans at both lumbosacral enlargement and cervical spinal cord. Modified Japanese Orthopedic Association (mJOA) score was also recorded for those with CSM. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of DTI in the two groups were compared. We also examined the correlation between DTI indices (ADC and FA) of the lumbosacral enlargement and those of the cervical spinal cord, and between DTI indices and mJOA in the CSM group. RESULTS: Compared with the values of healthy subjects, the ADC values of patients with CSM were significantly increased, and FA values were significantly decreased at both cervical spinal cord and lumbosacral enlargement. Changes in FA value of the cervical cord showed a positive correlation to those of the lumbosacral enlargement in the CSM group. Importantly, a linear correlation was detected between mJOA score and DTI indices (ADC and FA) of the cervical cord, as well as FA value of the lumbosacral enlargement in the CSM group. CONCLUSION: DTI indices, especially FA, of the lumbosacral enlargement correlate with clinical assessments of patients with CSM, and hence may be useful for evaluating the severity of cervical cord injury.

Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging.

OBJECTIVE: To investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health. METHODS: We identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population-based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline. RESULTS: All the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow-up times, and its primary impact was through cortical thinning. INTERPRETATION: We developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866-877.

Neuroimaging predictors of onset and course of depression in childhood and adolescence: A systematic review of longitudinal studies.

Major depressive disorder (MDD) often emerges during adolescence with detrimental effects on development as well as lifetime consequences. Identifying neurobiological markers that are associated with the onset or course of this disorder in childhood and adolescence is important for early recognition and intervention and, potentially, for the prevention of illness onset. In this systematic review, 68 longitudinal neuroimaging studies, from 34 unique samples, that examined the association of neuroimaging markers with onset or changes in paediatric depression published up to 1 February 2019 were examined. These studies employed different imaging modalities at baseline; structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI) or electroencephalography (EEG). Most consistent evidence across studies was found for blunted reward-related (striatal) activity (fMRI and EEG) as a potential biological marker for both MDD onset and course. With regard to structural brain measures, the results were highly inconsistent, likely caused by insufficient power to detect complex mediating effects of genetic and environmental factors in small sample sizes. Overall, there were a limited number of samples, and confounding factors such as sex and pubertal development were often not considered, whereas these factors are likely to be relevant especially in this age range.

Relationships Between Diffusion Tensor Imaging and Cerebrospinal Fluid Metrics in Early Stages of the Alzheimer's Disease Continuum.

Recently, the field of Alzheimer's disease (AD) research has adopted a new framework that places the progression of AD along a continuum consisting of a preclinical stage, followed by conversion to mild cognitive impairment, and ultimately dementia. Important neuropathological changes occur in the preclinical phase, necessitating the identification of metrics that can detect such early changes. While cerebrospinal fluid (CSF) measures of amyloid and tau are generally accepted as biomarkers of AD pathology, neuroimaging measures used to index white matter alterations throughout the brain remain less widely endorsed as candidate biomarkers. To explore the relationship between white matter alterations and AD pathology, we review the literature on multimodal studies that assessed both CSF markers and white matter indices, derived from diffusion tensor imaging (DTI) methods, across cohorts primarily in the early phases of AD. Our review indicates that abnormal CSF measures of Aß42 and tau are associated with widespread alterations in white matter microstructure throughout the brain. Furthermore, white matter variability is related to individual differences in behavior and can aid in tracking longitudinal changes in cognition. Our review advocates for the utilization of DTI metrics in investigations of early AD and suggests that the combined use of DTI and CSF markers may better explain individual differences in cognition and disease progression. However, further research is needed to resolve certain mixed findings.

Training-induced white matter microstructure changes in survivors of neonatal critical illness: A randomized controlled trial.

In a nationwide randomized controlled trial, white matter microstructure was assessed before and immediately after Cogmed Working-Memory Training (CWMT) in school-age neonatal critical illness survivors. Eligible participants were survivors (8-12 years) with an IQ ≥ 80 and a z-score of ≤ -1.5 on (working)memory test at first assessment. Diffusion Tensor Imaging was used to assess white matter microstructure. Associations between any training-induced changes and improved neuropsychological outcome immediately and one year post-CWMT were evaluated as well. The trial was conducted between October 2014-June 2017 at Erasmus MC-Sophia, Rotterdam, Netherlands. Researchers involved were blinded to group allocation. Participants were randomized to CWMT(n = 14) or no-intervention(n = 20). All children completed the CWMT. Global fractional anisotropy(FA) increased significantly post-CWMT compared to no-intervention(estimated-coefficient = .007, p = .015). Increased FA(estimated coefficient = .009, p = .033) and decreased mean diffusivity(estimated-coefficient = -.010, p = .018) were found in the left superior longitudinal fasciculus(SFL) post-CWMT compared no-intervention. Children after CWMT who improved with >1SD on verbal working-memory had significantly higher FA in the left SLF post-CWMT(n = 6; improvement = .408 ±â€¯.01) than children without this improvement post-CWMT(n = 6; no-improvement = .384 ±â€¯.02), F(1,12) = 6.22, p = .041, ηp2 = .47. No other structure-function relationships were found post-CWMT. Our findings demonstrate that white matter microstructure and associated cognitive outcomes are malleable by CWMT in survivors of neonatal critical illness.

Dopamine D2/D3 receptor abnormalities after traumatic brain injury and their relationship to post-traumatic depression.

OBJECTIVE: To investigate dopamine D2/D3 receptor availability following traumatic brain injury (TBI) and their relationship to the presence of DSM-IV Major Depressive Disorder (MDD) and patterns of axonal injury. METHODS: Twelve moderate-severe TBI patients and 26 controls were imaged using [11C]PHNO positron emission tomography (PET) and structural magnetic resonance imaging (MRI). TBI patients and a second group of 32 controls also underwent diffusion tensor imaging (DTI) and neuropsychological assessment. Patients included six with post-injury MDD (TBI-MDD) and six without (TBI-NON). Non-displaceable binding potential (BPND) [11C]PHNO values were used to index D2/D3 receptor availability, and were calculated using a reference region procedure. Differences in BPND were examined using voxelwise and region-of-interest analyses. White matter microstructure integrity, quantified by fractional anisotropy (FA), was assessed and correlated with BPND. RESULTS: Lower [11C]PHNO BPND was found in the caudate across all TBI patients when compared to controls. Lower [11C]PHNO BPND was observed in the caudate of TBI-MDD patients and increased [11C]PHNO BPND in the Amygdala of TBI-NON patients compared to controls. There were no significant differences in [11C]PHNO BPND between TBI-MDD and TBI-NON patients. Furthermore, DTI provided evidence of axonal injury following TBI. The uncinate fasciculus and cingulum had abnormally low FA, with the uncinate particularly affected in TBI-MDD patients. Caudate [11C]PHNO BPND correlated with FA within the nigro-caudate tract. CONCLUSIONS: [11C]PHNO BPND is abnormal following TBI, which indicates post-traumatic changes in D2/D3 receptors. Patterns of [11C]PHNO BPND seen in patients with and without MDD suggest that further research would be beneficial to determine whether the use of dopaminergic treatment might be effective in the treatment of post-traumatic depression.

White matter microstructural differences identified using multi-shell diffusion imaging in six-year-old children born very preterm.

INTRODUCTION: The underlying microstructural properties of white matter differences in children born very preterm (<32 weeks gestational age) can be investigated in depth using multi-shell diffusion imaging. The present study compared white matter across the whole brain using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics in children born very preterm and full-term children at six years of age. We also investigated associations between white matter microstructure with early brain injury and developmental outcomes. METHOD: Multi-shell diffusion imaging, T1-weighted anatomical MR images and developmental assessments were acquired in 23 children born very preterm (16 males; mean scan age: 6.57 ±â€¯0.34 years) and 24 full-term controls (10 males, mean scan age: 6.62 ±â€¯0.37 years). DTI metrics were obtained and neurite orientation dispersion index (ODI) and density index (NDI) were estimated using the NODDI diffusion model. FSL's tract-based spatial statistics were performed on traditional DTI metrics and NODDI metrics. Voxel-wise comparisons were performed to test between-group differences and within-group associations with developmental outcomes (intelligence and visual motor abilities) as well as early white matter injury and germinal matrix/intraventricular haemorrhage (GMH/IVH). RESULTS: In comparison to term-born children, the children born very preterm exhibited lower fractional anisotropy (FA) across many white matter regions as well as higher mean diffusivity (MD), radial diffusivity (RD), and ODI. Within-group analyses of the children born very preterm revealed associations between higher FA and NDI with higher IQ and VMI. Lower ODI was found within the corona radiata in those with a history of white matter injury. Within the full-term group, associations were found between higher NDI and ODI with lower IQ. CONCLUSION: Children born very preterm exhibit lower FA and higher ODI than full-term children. NODDI metrics provide more biologically specific information beyond DTI metrics as well as additional information of the impact of prematurity and white matter microstructure on cognitive outcomes at six years of age.

Microstructural neuroimaging of white matter tracts in persistent post-concussion syndrome: A prospective controlled cohort study.

INTRODUCTION: Children with mild traumatic brain injury (mTBI) typically recover quickly, however approximately 15% experience persistent post-concussive symptoms (PPCS) past 3 months. The microstructural pathology associated with underlying persistent symptoms is poorly understood but is suggested to involve axonal injury to white matter tracts. Diffusion tensor imaging (DTI) can be used to visualize and characterize damage to white matter microstructure of the brain. OBJECTIVE: We aimed to investigate white matter microstructure in children with persistent concussive symptoms as compared to typically developing controls, alongside evaluating differences in white matter changes over time and how this relates to symptom recovery. METHODS: The current study is a prospective, longitudinal, controlled cohort study of children with mTBI. 104 children aged 8 to 18 years with a mTBI (72 symptomatic; 32 asymptomatic) were recruited from the Alberta Children's Hospital and compared to 20 healthy controls. Microstructural evidence of white matter injury was evaluated using DTI one month post injury and repeated 4 to 6 weeks later. Primary outcomes included fractional anisotropy and mean diffusivity of the corticospinal tracts, uncinate fasciculi, and motor fibers of the corpus callosum. Post-concussive symptoms were also measured using the Post-Concussion Symptom Inventory (PCSI) taken at both time points. RESULTS: Fractional anisotropy of the left uncinate fasciculi was lower in symptomatic children compared to controls (F(2,119) = 3.582, p = 0.031). No other significant differences were observed. CONCLUSIONS: Our findings provide evidence of microstructural injury following mTBI in children with ongoing post-concussive symptoms one month post injury. The changes were persistent 4-6 weeks later. Further longitudinal studies of white matter microstructure in PPCS will be helpful to clarify whether these white matter alterations resolve over time.