White Matter Bundles Research Articles

The effect of the number of fibers in tractography reconstruction of white matter bundles.

The study of white matter (WM) through diffusion Magnetic Resonance Imaging (dMRI) is crucial to obtain a better understanding of human brain connections and functions, at a macroscopic level. A large number of works have focused on long range brain connections, while recently, several studies have also analyzed superficial WM connectivity. In recent years, with the massive use of HCP database, and its processing with known softwares like DSI Studio and MRtrix, it is necessary to evaluate the influence of tractography parameters on the reconstruction of fiber bundles and further analyses. We study the effect of the number of fibers, for whole brain tractography, on the reconstruction of deep and superficial WM bundles based on their segmentation using multi-subject bundle atlases. For DSI Studio (deterministic algorithm), a value of 1M fibers could reconstruct most of deep white matter (DWM) bundles, while a value of 1.5M was required for superficial white matter (SWM) bundles. In the case of MRtrix (probabilistic algorithm), a value of 3M fibers was found to be suitable for the study of both kinds of fibers. Furthermore, we found the tracking of SWM bundles to be more sensitive to several parameters than DWM, for DSI Studio.

Reducing variability in along-tract analysis with diffusion profile realignment

Diffusion weighted magnetic resonance imaging (dMRI) provides a non invasive virtual reconstruction of the brain's white matter structures through tractography. Analyzing dMRI measures along the trajectory of white matter bundles can provide a more specific investigation than considering a region of interest or tract-averaged measurements. However, performing group analyses with this along-tract strategy requires correspondence between points of tract pathways across subjects. This is usually achieved by creating a new common space where the representative streamlines from every subject are resampled to the same number of points. If the underlying anatomy of some subjects was altered due to, e.g., disease or developmental changes, such information might be lost by resampling to a fixed number of points. In this work, we propose to address the issue of possible misalignment, which might be present even after resampling, by realigning the representative streamline of each subject in this 1D space with a new method, coined diffusion profile realignment (DPR). Experiments on synthetic datasets show that DPR reduces the coefficient of variation for the mean diffusivity, fractional anisotropy and apparent fiber density when compared to the unaligned case. Using 100 in vivo datasets from the human connectome project, we simulated changes in mean diffusivity, fractional anisotropy and apparent fiber density. Independent Student's t-tests between these altered subjects and the original subjects indicate that regional changes are identified after realignment with the DPR algorithm, while preserving differences previously detected in the unaligned case. This new correction strategy contributes to revealing effects of interest which might be hidden by misalignment and has the potential to improve the specificity in longitudinal population studies beyond the traditional region of interest based analysis and along-tract analysis workflows.

White-matter commissures: a clinically focused anatomical review.

The objective of this review is to provide a structured approach to the main white matter commissures, their anatomic and radiological definition and disease implications. The Pubmed database and The JAMA Network were used for the literature review and the following terms were searched using Sort by: Best Match and Sort by: Most Recent: telencephalic commissure, forebrain commissure anatomy, fornix anatomy, commissure of fornix, posterior commissure, corpus callosum, commissural agenesis, Probst bundle, corpus callosum disorders review, corpus callosum diseases review, Marchiafava-Bignami, Alzheimer's disease and Forel commissure; 36 papers were selected, one excluded due to the language barrier. The interhemispheric communication in the brain is achieved via the brain commissures, bundles of white matter linking the two cerebral hemispheres. Anterior white commissure (AWC)-related with olfactory and non-visual communication, hippocampal commissure-main efferent pathway of the hippocampus, connecting the hippocampal formation to structures beyond the temporal lobe, crucial in declarative memory formation and consolidation-and the corpus callosum (CC)-from the anterior commissure to the hippocampal commissure-are the main telencephalic commissures. Supramammilary commissure, posterior commissure, supraoptic commissure and habenular commissure are diencephalic commissures-unknown function, probably related to involuntary eye movements. Commissural agenesis (AWC is absent or impossible to recognize), Alzheimer's Disease (hippocampal commissure may contribute for disease dissemination) and agenesis of corpus callosum are some of the disturbances that involve the telenchephalic commissures. A comprehensive understanding of the clinic-anatomic correlation is pivotal to understand the pathology and therefore improve our diagnostic accuracy and treatment options, in the background of all patient management.

Tractography and machine learning: Current state and open challenges

Supervised machine learning (ML) algorithms have recently been proposed as an alternative to traditional tractography methods in order to address some of their weaknesses. They can be path-based and local-model-free, and easily incorporate anatomical priors to make contextual and non-local decisions that should help the tracking process. ML-based techniques have thus shown promising reconstructions of larger spatial extent of existing white matter bundles, promising reconstructions of less false positives, and promising robustness to known position and shape biases of current tractography techniques. But as of today, none of these ML-based methods have shown conclusive performances or have been adopted as a de facto solution to tractography. One reason for this might be the lack of well-defined and extensive frameworks to train, evaluate, and compare these methods.In this paper, we describe several datasets and evaluation tools that contain useful features for ML algorithms, along with the various methods proposed in the recent years. We then discuss the strategies that are used to evaluate and compare those methods, as well as their shortcomings. Finally, we describe the particular needs of ML tractography methods and discuss tangible solutions for future works.

Probing demyelination and remyelination of the cuprizone mouse model using multimodality MRI.

Various studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking. To investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination. Prospective. A cuprizone mice model with an age-matched control group (n = 5), 4-week cuprizone exposure group followed by 9-week on a normal diet (n = 6), and a 13-week cuprizone exposure group (n = 6). 3D gradient recalled echo, T2 -weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T. Quantification of DTI metrics, quantitative susceptibility mapping (QSM), and T2 -weighted imaging intensity in major white matter bundles. Nonparametric permutation tests were used with a cluster-forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family-wise correction. In vivo susceptibility values increased from -11.7 to -0.7 ppb (P < 0.001) in CC and from -13.7 to -5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13-week cuprizone exposure. Ex vivo susceptibility values increased from -25.4 to 7.4 ppb (P < 0.001) in CC and from -41.6 to -15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel-based analysis. QSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T2 -weighted images and DTI metrics. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1852-1865.

A Missing Connection: A Review of the Macrostructural Anatomy and Tractography of the Acoustic Radiation.

The auditory system of mammals is dedicated to encoding, elaborating and transporting acoustic information from the auditory nerve to the auditory cortex. The acoustic radiation (AR) constitutes the thalamo-cortical projection of this system, conveying the auditory signals from the medial geniculate nucleus (MGN) of the thalamus to the transverse temporal gyrus on the superior temporal lobe. While representing one of the major sensory pathways of the primate brain, the currently available anatomical information of this white matter bundle is quite limited in humans, thus constituting a notable omission in clinical and general studies on auditory processing and language perception. Tracing procedures in humans have restricted applications, and the in vivo reconstruction of this bundle using diffusion tractography techniques remains challenging. Hence, a more accurate and reliable reconstruction of the AR is necessary for understanding the neurobiological substrates supporting audition and language processing mechanisms in both health and disease. This review aims to unite available information on the macroscopic anatomy and topography of the AR in humans and non-human primates. Particular attention is brought to the anatomical characteristics that make this bundle difficult to reconstruct using non-invasive techniques, such as diffusion-based tractography. Open questions in the field and possible future research directions are discussed.

Anatomy and white matter connections of the inferior frontal gyrus.

The inferior frontal gyrus (IFG) is involved in the evaluation of linguistic, interoceptive, and emotional information. A detailed understanding of its subcortical white matter anatomy could improve postoperative morbidity related to surgery in and around this gyrus. Through GQI-based fiber tracking validated by gross anatomical dissection as ground truth, we characterized the fiber tracts of the IFG based on relationships to other well-known neuroanatomic structures. Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for fiber tracking analysis. We evaluated the IFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts. We identified four major connections of the IFG: a white matter bundle corresponding the frontal aslant tract connecting to the superior frontal gyrus; the superior longitudinal fasciculus connecting to the inferior parietal lobule, lateral occipital area, posterior temporal areas, and the temporal pole; the inferior fronto-occipital fasciculus connecting to the cuneus and lingual gyrus; and the uncinate fasciculus connecting to the temporal pole. A callosal fiber bundle connecting the inferior frontal gyri bilaterally was also identified. The IFG is an important region implicated in a variety of tasks including language processing, speech production, motor control, interoceptive awareness, and semantic processing. Postsurgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study. Clin. Anat. 32:546-556, 2019. © 2019 Wiley Periodicals, Inc.

Nanoporous hollow fibers as a phantom material for the validation of diffusion magnetic resonance imaging

ABSTRACTDiffusion‐weighted magnetic resonance imaging (MRI) is an emerging noninvasive imaging modality. In this study, highly aligned, uniform, nanoporous, hollow polycaprolactone fibers were successfully synthesized in a single step to mimic the axon bundle structure in human white matter. Their porous nature, morphology, and physicochemical properties were carefully studied with respect to their suitability as a phantom material for brain imaging. The aligned fibrous bundles were then arranged into specific angles (30 and 90°), scanned, and evaluated with high‐resolution MRI fiber tractography. Diffusion tensor imaging and the tractography of fibers of five different structures at three temperatures were acquired and compared. Furthermore, an integrated brain phantom created from a combination of agar gel and aligned fibrous bundles was also fabricated and analyzed. The results demonstrate the excellent ability of the fibers to mimic the axonal bundles of brain white matter. The fibrous bundles were well mixed in the common agar phantom while retaining their fibrous configuration; this demonstrated their potential as brain white matter phantoms. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47617.

White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease.

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN-DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract- and atlas-based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.

Real-Time Ex-Vivo Magnetic Resonance Image—Guided Dissection of Human Brain White Matter: A Proof-of-Principle Study

Modern neuroanatomic education should be based on interdisciplinary methods that allow an understanding of the cerebral circuitry, which is at the base of the structural connectivity. Ex-vivo MRI-guided dissection is an essential method for developing and refining the knowledge of complex 3-dimensional brain anatomy and the mutual relationships between structures and architecture of the white matter bundles. The aim of this technical note is to present a new and innovative method of studying human brain white matter. Four adult human cerebral hemispheres were prepared according to the Klinger's method. T1-weighted and T2-weighted and fluid attenuated inversion recovery images were obtained with a 3T magnetic resonance machine. The dissection was performed in a dedicated neurosurgical laboratory equipped with a microscope and an electromagnetic neuronavigation system that guided the whole white matter dissection. Gyri and sulci morphology were studied in detail. The relations between superficial and inner structures were observed before and after the dissection. Gray matter was carefully removed with blunt dissectors, and the U-fibers were exposed. Afterwards, deeper association and projection fibers, such as the arcuate fasciculus, superior and inferior longitudinal fasciculus, corona radiata, extreme and external capsule, claustrum, anterior commissure, and internal capsule were visualized under high magnification. The neuronavigation system was crucial for continuously checking the whole dissection procedure to avoid any accidental excision of fibers. Image-guided neuronavigated dissection can significantly improve the quality of white matter dissection and represents a valid tool for learning the 3-dimensional anatomy of the human brain tracts.

Abstract TMP120: Sildenafil Treatment of Vascular Dementia in Aged Rats

Background and Purpose: Vascular Dementia (VaD) caused by silent or mini strokes, affects cognition and memory predominantly in the elderly. Sildenafil, a cGMP-specific phosphodiesterase type 5 inhibitor mediates vasodilation. In this study, we tested the therapeutic effects of Sildenafil on cognitive decline, white matter (WM) damage, autophagy and inflammatory response associated with a model of VaD in aged rats. Methods: Male, 16-18 month old Wistar rats were subjected to a multiple microinfarction (MMI) induced VaD model and were treated daily with or without Sildenafil (2mg/Kg, i.p) starting at 24 hours after MMI for 28 days (n=7/group). A battery of cognitive tests was performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation, Western blot and PCR assays. Results: Compared to aged-control, aged-MMI rats exhibit significant (p&lt;0.05): 1) short term memory loss, long term memory deficits and anxiety like behavior, respectively; 2) increased brain inflammatory factor expression such as IL-1β, MCP-1 and thrombin; 3) increased brain WM/axonal damage as well as increased autophagy in the brain. Compared to aged-MMI control rats, Sildenafil treatment in aged-MMI rats significantly (p&lt;0.05): 1) improves short and long term memory as well as decreases anxiety like behavior; 2) improves spatial learning and memory; 3) increases axon and myelin density in the corpus callosum and white matter bundles in the striatum; 4) increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum; 5), increases synaptic protein expression in the cortex and striatum as well as increases water channel protein Aquaporin-4 expression around cerebral blood vessels; 6) decreases inflammatory factors MCP-1, IL-1β and thrombin expression as well as decreases MMI induced autophagy indicated by LC3A and Beclin-1 expression. Conclusions: MMI in aged rats induces significant WM damage, autophagy, and inflammatory responses which lead to decline in cognition and memory. Sildenafil treatment increases white matter remodeling, synaptic plasticity, decreases autophagy and exerts anti-inflammatory effects which in concert may contribute to the improvement in cognition and memory.

Sildenafil treatment of vascular dementia in aged rats

Backgroundand purpose: In this study, we employed a multiple microinfarction (MMI) based vascular dementia (VaD) model in aged rats and tested the therapeutic effects of Sildenafil, a phosphodiesterase type 5 inhibitor, on cognitive decline, white matter damage, autophagy and inflammatory response associated with VaD. MethodsMale, aged (16–18 months) Wistar rats were subjected to MMI (800 ± 100, 70–100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days. Four experimental groups were employed: Sham control, Sham + Sildenafil, MMI, and MMI + Sildenafil. A battery of cognitive tests were performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation and PCR assay. ResultsSildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats. Sildenafil treatment of aged MMI rats significantly increases axon and myelin density in the corpus callosum and white matter bundles in the striatum, increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum, and increases synaptic protein expression in the cortex and striatum compared to aged control MMI rats. In addition, Sildenafil treatment of MMI in aged rats significantly decreases Beclin1 expression and inflammatory factors Monocyte chemoattractant protein-1 and Interleukin-1β expression in brain. Sildenafil treatment in aged rats does not improve cognitive outcome compared to aged sham control rats. ConclusionsSildenafil treatment of MMI in aged rats significantly improves cognition and memory at 1 month after MMI. Sildenafil treatment increases axon and myelin density, increases Synaptophysin expression, decreases autophagic activity and exerts anti-inflammatory effects which in concert may contribute to cognitive improvement in aged rats subjected to MMI.

Concurrent analysis of white matter bundles and grey matter networks in the chimpanzee

Understanding the phylogeny of the human brain requires an appreciation of brain organization of our closest animal relatives. Neuroimaging tools such as magnetic resonance imaging (MRI) allow us to study whole-brain organization in species which can otherwise not be studied. Here, we used diffusion MRI to reconstruct the connections of the cortical hemispheres of the chimpanzee. This allowed us to perform an exploratory analysis of the grey matter structures of the chimpanzee cerebral cortex and their underlying white matter connectivity profiles. We identified a number of networks that strongly resemble those found in other primates, including the corticospinal system, limbic connections through the cingulum bundle and fornix, and occipital–temporal and temporal–frontal systems. Notably, chimpanzee temporal cortex showed a strong resemblance to that of the human brain, providing some insight into the specialization of the two species’ shared lineage.

Correlations between cervical spinal cord magnetic resonance diffusion tensor and diffusion kurtosis imaging metrics and motor performance in patients with chronic ischemic brain lesions of the corticospinal tract.

To investigate modifications of Magnetic Resonance Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) metrics in lateral white matter (WM) bundles of the cervical spinal cord in patients with previous stroke in the vascular territory of the middle cerebral artery (MCA). Twenty consecutive patients with a previous ischemic stroke of the MCA territory and a varying degree of upper motor impairment were enrolled. DKI was centered at the C3C4 and C5C6 intervertebral level. The fractional anisotropy (FA) values in C3C4 and C5C6 were found to be significantly lower in the lateral WM bundles contralateral to the ischemic lesion and thus, in the WM bundle including the affected corticospinal tract (CST) (p = 0.005 and p = 0.008, respectively), as well as mean kurtosis (MK) and axonal water fraction (AWF) values (p = 0.004 and p = 0.04. respectively). FA values correlated significantly with the Global Motor Index (GMI) both for C3C4 (ρ = 0.61, p = 0.004) and C5C6 (ρ = 0.69, p = 0.002). At C3C4, AWF correlated significantly with GMI (ρ = 0.54, p = 0.03). No correlations were found between lateral WM bundle volumes and GMI. A reduction of anisotropy and microstructural complexity in the affected lateral WM bundle of the cervical spinal cord was observed in patients with previous ischemic stroke involving the CST. The correlations between these metrics and motor performance were statistically significant.

Individual white matter bundle trajectories are associated with deep brain stimulation response in obsessive-compulsive disorder

BackgroundThe ventral anterior limb of the internal capsule (vALIC) is a target for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD). Conventional surgical planning is based on anatomical landmarks.Objective/hypothesis: We hypothesized that treatment response depends on the location of the active DBS contacts with respect to individual white matter bundle trajectories. This study thus aimed to elucidate whether vALIC DBS can benefit from bundle-specific targeting. MethodsWe performed tractography analysis of two fiber bundles, the anterior thalamic radiation (ATR) and the supero-lateral branch of the medial forebrain bundle (MFB), using diffusion-weighted magnetic resonance imaging (DWI) data. Twelve patients (10 females) who had received bilateral vALIC DBS for at least 12 months were included. We related the change in OCD symptom severity on the Yale-Brown obsessive-compulsive scale (Y-BOCS) between baseline and one-year follow-up with the distances from the active contacts to the ATR and MFB. We further analyzed the relation between treatment response and stimulation sites in standard anatomical space. ResultsWe found that active stimulation of the vALIC closer to the MFB than the ATR was associated with better treatment outcome (p = 0.04; r2 = 0.34). In standard space, stimulation sites were largely overlapping between treatment (non)responders, suggesting response is independent of the anatomically defined electrode position. ConclusionThese findings suggest that vALIC DBS for OCD may benefit from MFB-specific implantation and highlight the importance of corticolimbic connections in OCD response to DBS. Prospective investigation is necessary to validate the clinical use of MFB targeting.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

Bundle-specific tractography with incorporated anatomical and orientational priors

Anatomical white matter bundles vary in shape, size, length, and complexity, making diffusion MRI tractography reconstruction of some bundles more difficult than others. As a result, bundles reconstruction often suffers from a poor spatial extent recovery. To fill-up the white matter volume as much and as best as possible, millions of streamlines can be generated and filtering techniques applied to address this issue. However, well-known problems and biases are introduced such as the creation of a large number of false positives and over-representation of easy-to-track parts of bundles and under-representation of hard-to-track.To address these challenges, we developed a Bundle-Specific Tractography (BST) algorithm. It incorporates anatomical and orientational prior knowledge during the process of streamline tracing to increase reproducibility, sensitivity, specificity and efficiency when reconstructing certain bundles of interest. BST outperforms classical deterministic, probabilistic, and global tractography methods. The increase in anatomically plausible streamlines, with larger spatial coverage, helps to accurately represent the full shape of bundles, which could greatly enhance and robustify tract-based and connectivity-based neuroimaging studies.

Macroscale White Matter Alterations Due to Traumatic Cerebral Microhemorrhages Are Revealed by Diffusion Tensor Imaging.

With the advent of susceptibility-weighted imaging (SWI), the ability to identify cerebral microbleeds (CMBs) associated with mild traumatic brain injury (mTBI) has become increasingly commonplace. Nevertheless, the clinical significance of post-traumatic CMBs remains controversial partly because it is unclear whether mTBI-related CMBs entail brain circuitry disruptions which, although structurally subtle, are functionally significant. This study combines magnetic resonance and diffusion tensor imaging (MRI and DTI) to map white matter (WM) circuitry differences across 6 months in 26 healthy control volunteers and in 26 older mTBI victims with acute CMBs of traumatic etiology. Six months post-mTBI, significant changes (p < 0.001) in the mean fractional anisotropy of perilesional WM bundles were identified in 21 volunteers, and an average of 47% (σ = 21%) of TBI-related CMBs were associated with such changes. These results suggest that CMBs can be associated with lasting changes in perilesional WM properties, even relatively far from CMB locations. Future strategies for mTBI care will likely rely on the ability to assess how subtle circuitry changes impact neural/cognitive function. Thus, assessing CMB effects upon the structural connectome can play a useful role when studying CMB sequelae and their potential impact upon the clinical outcome of individuals with concussion.

Local Injection of Endothelin-1 in the Early Neonatal Rat Brain Models Ischemic Damage Associated with Motor Impairment and Diffuse Loss in Brain Volume

Cerebral palsy is an irreversible movement disorder resulting from cerebral damage sustained during prenatal or neonatal brain development. As survival outcomes for preterm injury improve, there is increasing need to model ischemic injury at earlier neonatal time-points to better understand the subsequent pathological consequences. Here we demonstrate a novel neonatal ischemic model using focal administration of the potent vasoconstrictor peptide, endothelin-1 (ET-1), in newborn rats. The functional and histopathological outcomes compare favourably to those reported following the widely used hypoxic ischemia (HI) model. These include a robust motor deficit sustained into adulthood and recapitulation of hallmark features of preterm human brain injury, including atrophy of subcortical white matter and periventricular fiber bundles. Compared to procedures involving carotid artery manipulation and periods of hypoxia, the ET-1 ischemia model represents a rapid and technically simplified model more amenable to larger cohorts and with the potential to direct the locus of ischemic damage to specific brain areas.

Analysis of fractional anisotropy and mean diffusivity in refractory and non-refractory idiopathic generalized epilepsies

PurposeTo compare white matter bundles and fiber tract changes in seizure-free and non-seizure-free idiopathic generalized epilepsy (IGE) patients. MethodForty adult patients with IGE underwent a 3 T brain MRI with DTI sequences. According to seizure control status, eighteen patients were classified as refractory (R) if they had presented at least one incapacitating seizure in the previous six months, while on appropriate antiepileptic drug treatment. Twenty two seizure-free patients with adequate seizure control were considered non-refractory (NR). We compared fractional anisotropy (FA) and mean diffusivity (MD) values in sixteen white matter tracts in the R and NR groups, and in twenty healthy subjects. ResultsR and NR groups did not differ in gender, age and education. We found decreased FA in two tracts in the R group (forceps major and right uncinate fasciculus) and approaching statistical significance in two tracts in the NR group (right cingulate gyrus and right uncinate fasciculus) group, as well as increased MD in six tracts in the R group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi, and right cingulate gyrus) and in five tracts in the NR group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi), compared to controls. No differences were noted comparing FA and MD values between R and NR groups. ConclusionsIn our patient population, refractory IGE patients on adequate antiepileptic drug treatment did not present more severe white matter tract involvement compared to non-refractory patients.