Yi Lao

A Multivariate Surface-Based Analysis of the Putamen in Premature Newborns: Regional Differences within the Ventral Striatum

Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates.

Neuroimaging Changes in the Brain in Contact versus Noncontact Sport Athletes Using Diffusion Tensor Imaging

OBJECTIVE Traumatic brain injury in contact sports has significant impact on short-term neurologic and neurosurgical function as well as longer-term cognitive disability. In this study, we aim to demonstrate that contact sport participants exhibit differences in diffusion tensor imaging (DTI) caused by repeated physical impacts on the brain. We also aim to determine that impact incurred by the contact sports athletes during the season may result in the differences between the pre- and postseason DTI scans. METHODS DTI data were collected from 10 contact-sport (mean age 20.4 ± 1.36 years) and 13 age-matched noncontact-sport (mean age 19.5 ± 1.03 years) male athletes on a 3-Tesla magnetic resonance imaging scanner. A single-shot, echo-planar imaging sequence with b-value of 1000 s/mm(2) and 25 gradient directions was used. Eight of the athletes were again scanned after the end of the season. The b0 nondiffusion-weighted image was averaged five times. Voxel-wise, two-sample t tests were run for all group comparisons, and in each case, the positive false-discovery rate was computed to assess the whole-map, multiple-comparison corrected significance. RESULTS There were significant differences in the fractional anisotropy values in the inferior fronto-occipital fasciculus, parts of the superior and posterior coronal radiate, and the splenium of the corpus callosum (CC) as well as smaller clusters in the genu and parts of the body of the CC. In addition, the external capsule also shows some difference between the contact and noncontact athlete brains. In addition, the preseason and postseason showed differences in these regions, however, the postseason P-values show significance in more areas of the CC. CONCLUSIONS There are significant DTI changes in the CC, the external capsule, the inferior fronto-occipital fasciculus, as well as regions such as the superior/posterior corona radiata the preseason contact versus the noncontact control athletes were compared and also when the postseason contact athletes with the control athletes were compared.

A T1 and DTI fused 3D corpus callosum analysis in pre- vs. post-season contact sports players

Sports related traumatic brain injury (TBI) is a worldwide public health issue, and damage to the corpus callosum (CC) has been considered as an important indicator of TBI. However, contact sports players suffer repeated hits to the head during the course of a season even in the absence of diagnosed concussion, and less is known about their effect on callosal anatomy. In addition, T1-weighted and diffusion tensor brain magnetic resonance images (DTI) have been analyzed separately, but a joint analysis of both types of data may increase statistical power and give a more complete understanding of anatomical correlates of subclinical concussions in these athletes. Here, for the first time, we fuse T1 surface-based morphometry and a new DTI analysis on 3D surface representations of the CCs into a single statistical analysis on these subjects. Our new combined method successfully increases detection power in detecting differences between pre- vs. post-season contact sports players. Alterations are found in the ventral genu, isthmus, and splenium of CC. Our findings may inform future health assessments in contact sports players. The new method here is also the first truly multimodal diffusion and T1-weighted analysis of the CC, and may be useful to detect anatomical changes in the corpus callosum in other multimodal datasets.

A study of brain white matter plasticity in early blinds using tract-based spatial statistics and tract statistical analysis

Early blind individuals are known to exhibit structural brain reorganization. Particularly, early-onset blindness may trigger profound brain alterations that affect not only the visual system but also the remaining sensory systems. Diffusion tensor imaging (DTI) allows in-vivo visualization of brain white matter connectivity, and has been extensively used to study brain white matter structure. Among statistical approaches based on DTI, tract-based spatial statistics (TBSS) is widely used because of its ability to automatically perform whole brain white matter studies. Tract specific analysis (TSA) is a more recent method that localizes changes in specific white matter bundles. In the present study, we compare TBSS and TSA results of DTI scans from 12 early blind individuals and 13 age-matched sighted controls, with two aims: (a) to investigate white matter alterations associated with early visual deprivation; (b) to examine the relative sensitivity of TSA when compared with TBSS, for both deficit and hypertrophy of white matter microstructures. Both methods give consistent results for broad white matter regions of deficits. However, TBSS does not detect hypertrophy of white matter, whereas TSA shows a higher sensitivity in detecting subtle differences in white matter colocalized to the posterior parietal lobe.

Impact of Early and Late Visual Deprivation on the Structure of the Corpus Callosum: A Study Combining Thickness Profile with Surface Tensor-Based Morphometry

Blindness represents a unique model to study how visual experience may shape the development of brain organization. Exploring how the structure of the corpus callosum (CC) reorganizes ensuing visual deprivation is of particular interest due to its important functional implication in vision (e.g., via the splenium of the CC). Moreover, comparing early versus late visually deprived individuals has the potential to unravel the existence of a sensitive period for reshaping the CC structure. Here, we develop a novel framework to capture a complete set of shape differences in the CC between congenitally blind (CB), late blind (LB) and sighted control (SC) groups. The CCs were manually segmented from T1-weighted brain MRI and modeled by 3D tetrahedral meshes. We statistically compared the combination of local area and thickness at each point between subject groups. Differences in area are found using surface tensor-based morphometry; thickness is estimated by tracing the streamlines in the volumetric harmonic field. Group differences were assessed on this combined measure using Hotelling’s T2 test. Interestingly, we observed that the total callosal volume did not differ between the groups. However, our fine-grained analysis reveals significant differences mostly localized around the splenium areas between both blind groups and the sighted group (general effects of blindness) and, importantly, specific dissimilarities between the LB and CB groups, illustrating the existence of a sensitive period for reorganization. The new multivariate statistics also gave better effect sizes for detecting morphometric differences, relative to other statistics. They may boost statistical power for CC morphometric analyses.

Mapping the basal ganglia alterations in children chronically exposed to manganese

Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children.

A T1 and DTI fused 3D corpus callosum analysis in MCI subjects with high and low cardiovascular risk profile

Understanding the extent to which vascular disease and its risk factors are associated with prodromal dementia, notably Alzheimers disease (AD), may enhance predictive accuracy as well as guide early interventions. One promising avenue to determine this relationship consists of looking for reliable and sensitive in-vivo imaging methods capable of characterizing the subtle brain alterations before the clinical manifestations. However, little is known from the imaging perspective about how risk factors such as vascular disease influence AD progression. Here, for the first time, we apply an innovative T1 and DTI fusion analysis of 3D corpus callosum (CC) on mild cognitive impairment (MCI) populations with different levels of vascular profile, aiming to de-couple the vascular factor in the prodromal AD stage. Our new fusion method successfully increases the detection power for differentiating MCI subjects with high from low vascular risk profiles, as well as from healthy controls. MCI subjects with high and low vascular risk profiles showed differed alteration patterns in the anterior CC, which may help to elucidate the inter-wired relationship between MCI and vascular risk factors.

Statistical Analysis of Relative Pose of the Thalamus in Preterm Neonates

Preterm neonates are at higher risk of neurocognitive and neurosensory abnormalities. While numerous studies have looked at the effect of prematurity on brain anatomy, none to date have attempted to understand the relative pose of subcortical structures and to assess its potential as a biomarker of abnormal growth. Here, we perform the first relative pose analysis on a point distribution model (PDM) of the thalamus between 17 preterm and 19 term-born healthy neonates. Initially, linear registration and constrained harmonic registration were computed to remove the irrelevant global pose information and obtain correspondence in vertices. All the parameters for the relative pose were then obtained through similarity transformation. Subsequently, all the pose parameters (scale, rotation and translation) were projected into a log-Euclidean space, where univariate and multivariate statistics were performed. Our method detected relative pose differences in the preterm birth for the left thalamus. Our results suggest that relative pose in subcortical structures is a useful indicator of brain injury, particularly along the anterior surface and the posterior surface. Our study supports the concept that there are regional thalamic asymmetries in the preterm that may be related to subtle white matter injury, have prognostic significance, or be related to preterm birth itself.

3D pre- versus post-season comparisons of surface and relative pose of the corpus callosum in contact sport athletes

Mild traumatic brain injury (MTBI) or concussive injury affects 1.7 million Americans annually, of which 300,000 are due to recreational activities and contact sports, such as football, rugby, and boxing[1]. Finding the neuroanatomical correlates of brain TBI non-invasively and precisely is crucial for diagnosis and prognosis. Several studies have shown the in influence of traumatic brain injury (TBI) on the integrity of brain WM [2-4]. The vast majority of these works focus on athletes with diagnosed concussions. However, in contact sports, athletes are subjected to repeated hits to the head throughout the season, and we hypothesize that these have an influence on white matter integrity. In particular, the corpus callosum (CC), as a small structure connecting the brain hemispheres, may be particularly affected by torques generated by collisions, even in the absence of full blown concussions. Here, we use a combined surface-based morphometry and relative pose analyses, applying on the point distribution model (PDM) of the CC, to investigate TBI related brain structural changes between 9 pre-season and 9 post-season contact sport athlete MRIs. All the data are fed into surface based morphometry analysis and relative pose analysis. The former looks at surface area and thickness changes between the two groups, while the latter consists of detecting the relative translation, rotation and scale between them.

Ventricular shape and relative position abnormalities in preterm neonates

Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM). This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.