Neurite Orientation Dispersion Index Research Articles

Abstract 9: Pervasive White Matter Microstructure Dysintegrity Related To High Blood Pressure Among Asymptomatic Population

Background: Blood pressure is the strongest contributor to clinically evident cerebrovascular disease. We investigated the role of blood pressure on white matter (WM) microstructure among asymptomatic individuals without clinically evident cerebrovascular disease. Methods: We conducted a nested study within the UK Biobank, restricting our analysis to participants without cerebrovascular disease or dementia and with available brain diffusion tensor imaging (DTI). We tested for association between systolic blood pressure (SBP) and six different DTI metrics: fractional anisotropy (FA), mean diffusivity (MD), tensor mode (MO), intra-cellular volume fraction (ICVF), isotropic or free water volume fraction (ISOVF), and orientation dispersion index (OD) across 48 WM tracts using multivariable linear regression adjusted for potential confounders. We used Bonferroni-corrected p-values (0.05/48) for statistical significance. Results: We analyzed 33,440 participants. Mean age was 63.0 (SD 7.7), and 17,688 (53%) were female. Higher SBP is independently associated with pervasive decrease in FA and ICVF and increase in MD (Figure), after adjustment for vascular risk-factors. SBP was also associated with lower neurite OD (a more specific metric of axonal damage) in bilateral posterior corona radiata, external capsule, medial lemniscus, and corticospinal tracs. FA and OD of external capsule and posterior corona radiata had the largest drop per 10 mmHg increase of SBP (steepest slope). Conclusions: Higher SBP is associated with pervasive WM microstructure dysintegrity in asymptomatic individuals without evident cerebrovascular disease. DTI metrics of the posterior corona radiata and external capsule are most reflective of variations in SBP and may provide a potential biomarker to assess subtle WM microstructural damage in hypertensive patients or monitor treatment response in clinical trials.

Abnormal neurite density and orientation dispersion in frontal lobe link to elevated hyperactive/impulsive behaviours in young adults with traumatic brain injury.

Traumatic brain injury is a major public health concern. A significant proportion of individuals experience post-traumatic brain injury behavioural impairments, especially in attention and inhibitory control domains. Traditional diffusion-weighted MRI techniques, such as diffusion tensor imaging, have provided tools to assess white matter structural disruptions reflecting the long-term brain tissue alterations associated with traumatic brain injury. The recently developed neurite orientation dispersion and density imaging is a more advanced diffusion MRI modality, which provides more refined characterization of brain tissue microstructures by assessing the neurite orientation dispersion and neurite density properties. In this study, neurite orientation dispersion and density imaging data from 44 young adults with chronic traumatic brain injury (who had no prior-injury diagnoses of any sub-presentation of attention deficits/hyperactivity disorder or experience of severe inattentive and/or hyperactive behaviours) and 45 group-matched normal controls were investigated, to assess the post-injury morphometrical and microstructural brain alterations and their relationships with the behavioural outcomes. Maps of fractional anisotropy, neurite orientation dispersion index and neurite density index were calculated. Vertex-wise and voxel-wise analyses were conducted for grey matter and white matter, respectively. Post hoc region-of-interest-based analyses were also performed. Compared to the controls, the group of traumatic brain injury showed significantly increased orientation dispersion index and significantly decreased neurite density index in various grey matter regions, as well as significantly decreased orientation dispersion index in several white matter regions. Brain–behavioural association analyses indicated that the reduced neurite density index of the left precentral gyrus and the reduced orientation dispersion index of the left superior longitudinal fasciculus were significantly associated with elevated hyperactive/impulsive symptoms in the patients with traumatic brain injury. These findings suggest that post-injury chronical neurite intracellular volume and angular distribution anomalies in the frontal lobe, practically the precentral area, can significantly contribute to the onset of hyperactive/impulsive behaviours in young adults with traumatic brain injury.

White matter alterations and cognitive outcomes in children born very low birth weight

BackgroundVery low birth weight (VLBW) infants are at risk for disrupted white matter maturation, yet little is known about the contributing factors, particularly at preschool-age when cognitive difficulties begin to emerge. We examined white matter microstructure in five-year-old VLBW and full-term (FT) children, and its association with cognitive outcomes and birth weight. MethodsMulti-shell diffusion and MR images were obtained for 41 VLBW (mean birth weight: 1028.6 ± 256.8 g) and 26 FT (3295.4 ± 493.9 g) children. Fractional anisotropy (FA), radial diffusivity (RD), neurite orientation dispersion index (ODI) and density index (NDI) were estimated using diffusion tensor and neurite orientation dispersion and density imaging models. Between-group analyses used a general linear model with group and sex as explanatory variables. Within-group associations between white matter microstructure, cognitive outcomes and birth weight were also investigated. ResultsVLBW compared to FT children showed lower FA and NDI across widespread white matter regions. Smaller clusters of atypical ODI were also found in VLBW children. Within-group analyses in FT children revealed that lower RD and higher NDI were associated with vocabulary acquisition and working memory. In VLBW children, higher FA and NDI, and lower RD and ODI, were associated with improved processing speed. In both groups, FA was positively associated with birth weight. ConclusionsOur findings demonstrate white matter alterations in young VLBW children, including widespread reductions in axon density that may reflect sustained myelination disruptions. The associations with cognitive outcomes may also highlight which of the VLBW children are at higher risk for later cognitive difficulties.

Dendrite complexity of the posterior cingulate cortex as a substrate for recovery from post-stroke depression: A pilot study

The neural basis of recovery from a depressive state remains poorly understood. The main purpose of this study was to determine the neural basis of vulnerability/resilience to depression in stroke patients in terms of changes in regional microstructure. The study included 20 individuals with acute ischaemic stroke. Symptoms of depression were assessed, and the intraneurite volume fraction and neurite orientation-dispersion index (ODI) were evaluated by a multi-shell diffusion imaging and neurite-orientation dispersion and density imaging model. Patients underwent follow-up examinations after 2 months and were classified into depression improvement and depression deterioration groups. A significant interaction effect of group × time on the ODI was shown by voxel-based analysis in the posterior cingulate cortex (PCC). The ODI change in the PCC was negatively correlated with the change in the depression scale scores at the 2-month time point. The increase in ODI in the PCC that occurred during the 2-month interval was thought to be associated with decreased depressive symptom scores. As the ODI represents the pattern of sprawling dendrite progression, our findings indicate that the dendritic complexity of the PCC is a substrate for recovery in individuals who experienced post-stroke psychosocial and biological stress.

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

IntroductionThe 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.MethodMulti-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 ± 0.34 years) and 24 full-term controls (10 males, mean scan age: 6.62 ± 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).ResultsIn 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.ConclusionChildren 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.

White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.

Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7–63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test—retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI.

Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.

As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo.

Assessing white matter microstructure of the newborn with multi-shell diffusion MRI and biophysical compartment models

Brain white matter connections have become a focus of major interest with important maturational processes occurring in newborns. To study the complex microstructural developmental changes in-vivo, it is imperative that non-invasive neuroimaging approaches are developed for this age-group.Multi-b-value diffusion weighted imaging data were acquired in 13 newborns, and the biophysical compartment diffusion models CHARMED-light and NODDI, providing new microstructural parameters such as intra-neurite volume fraction (νin) and neurite orientation dispersion index (ODI), were developed for newborn data. Comparative analysis was performed and twenty ROIs in the white matter were investigated. Diffusion tensor imaging and both biophysical compartment models highlighted the compact and oriented structure of the corpus-callosum with the highest FA and νin values and the smallest ODI values. We could clearly differentiate, using the FA, νin and ODI, the posterior and anterior internal capsule representing similar cellular structure but with different maturation (i.e. partially myelinated and absence of myelin, respectively). Late maturing regions (external capsule and periventricular crossroads of pathways) had lower νin values, but displayed significant differences in ODI. The compartmented models CHARMED-light and NODDI bring new indices corroborating the cellular architectures, with the lowest νin, reflecting the late maturation of areas with thin non-myelinated fibers, and with highest ODI indicating the presence of fiber crossings and fanning.The application of biophysical compartment diffusion models adds new insights to the brain white matter development in vivo.