Nerve Fibers In White Matter Research Articles

An extensible hierarchical graph convolutional network for early Alzheimer’s disease identification

Background and Objective: For early identification of Alzheimer’s disease (AD) based on multi-modal magnetic resonance imaging (MRI) data, it is important to make comprehensive use of image features and non-image information to analyze the gray matter atrophy and the structural/functional connectivity abnormalities for different courses of AD.Methods: In this study, we propose an extensible hierarchical graph convolutional network (EH-GCN) for early AD identification. Based on the extracted image features from multi-modal MRI data using the presented multi-branch residual network (ResNet), the brain regions-of-interests (ROIs) based GCN is built to extract structural and functional connectivity features between different ROIs of the brain. In order to further improve the performance of AD identification, an optimized spatial GCN is proposed as convolution operator in the population-based GCN to avoid rebuilding the graph network and take advantage of relationships between subjects. Finally, the proposed EH-GCN is built by embedding the image features and internal brain connectivity features into the spatial population-based GCN, which provides an extensible way to improve early AD identification performance by adding imaging features and non-image information from multi-modal data.Results: Experiments are performed on two datasets, which illustrate the effectiveness of the extracted structural/functional connectivity features and the high computational efficiency of the proposed method. The classification accuracy of AD vs NC, AD vs MCI and MCI vs NC classification tasks reaches 88.71%, 82.71% and 79.68% respectively. The extracted connectivity features between ROIs indicate that functional abnormalities are earlier than gray matter atrophy and abnormalities of structural connections, which is consistent with the clinical manifestations. The proposed method allows for the addition of other modal image features and non-image information from multi-modal data to continuously improve the performance of clinical data analysis.Conclusions: The proposed method can help us comprehensively analyze the role of gray matter atrophy, the damage of white matter nerve fiber tracts and the degradation of functional connectivity for different courses of AD, which could be useful for further extraction of clinical biomarkers for early AD identification.

An analysis of the microstructure of white matter in migrain: a pilot study

White matter microstructure imaging has long been studied and analyzed with tensor diffusion pulse sequences. White matter integrity analysis has been performed on many different groups of cranial neuropathies. Migraine is a typical unilateral pulsating headache disorder. Although the prevalence of migraine is very high, the pathophysiology is still unclear. From the hypothesis, migraine and persistent migraine may affect the white matter microstructure image. Based on the diffusion of water molecules in the white matter nerve fiber bundle, and the connection to the “pain matrix”. Tract-based spatial statistics (TBSS) can demonstrate whether or not there is a difference in the water diffusion characteristics of fiber bundles in migraine patients compared with healthy volunteers. We conducted a pilot study to understand the TBSS analysis and white matter microstructure analysis in patients diagnosed with migraine. Key words: migrain, microstructures, white matter intergrity, DTI, TBSS

Correlation Between Learning and Memory Impairment and Changes in Cerebral White Matter Nerve Fibers and Pericytes in Rats with Chronic Cerebral Ischemia

Correlation Between Learning and Memory Impairment and Changes in Cerebral White Matter Nerve Fibers and Pericytes in Rats with Chronic Cerebral Ischemia

White matter degeneration in diffuse axonal injury and mild traumatic brain injury observed with automatic tractography.

A better understanding of white matter tract damage in patients with diffuse axonal injury (DAI) and mild traumatic brain injury (MTBI) is important to obtain an objective basis for sequelae. The purpose of this study was to clarify the characteristics of white matter tract degeneration in DAI and MTBI using automated tractography. T1-weighted and diffusion tensor imaging (DTI) was performed on seven DAI and seven MTBI patients as well as on nine healthy subjects. Automated probabilistic tractography analysis was performed using FreeSurfer and TRACULA (tracts constrained by underlying anatomy) for the reconstruction of major nerve fibers. We investigated the difference between DTI quantitative values in each white matter nerve fiber between groups and attempted to evaluate the classification accuracy of DAI and MTBI using receiver operator curve analysis. Both DAI and MTBI appeared to exhibit axonal degeneration along the nerve fiber tract in a scattered manner. The mean diffusivity of the ampulla of the corpus callosum was significantly higher in DAI than that in MTBI patients, suggesting axonal degeneration of the corpus callosum in DAI patients. Using mean diffusivity of the right cingulum-angular bundle, DAI and MTBI could be discriminated with an area under the curve of 94%. Both DAI and MTBI exhibited scattered axonal degeneration; however, DAI appeared to exhibit more pronounced axonal degeneration in the ampulla of the corpus callosum than MTBI. Our results suggest that DAI and MTBI can be accurately distinguished using DTI.

Age is reflected in the Fractal Dimensionality of MRI Diffusion Based Tractography

Fractal analysis is a widely used tool to analyze the geometrical complexity of biological structures. The geometry of natural objects such as plants, clouds, cellular structures, blood vessel, and many others cannot be described sufficiently with Euclidian geometric properties, but can be represented by a parameter called the fractal dimension. Here we show that a specific estimate of fractal dimension, the correlation dimension, is able to describe changes in the structural complexity of the human brain, based on data from magnetic resonance diffusion imaging. White matter nerve fiber bundles, represented by tractograms, were analyzed with regards to geometrical complexity, using fractal geometry. The well-known age-related change of white matter tissue was used to verify changes by means of fractal dimension. Structural changes in the brain were successfully be observed and quantified by fractal dimension and compared with changes in fractional anisotropy.

Teratogenic effects of Khat (Catha edulis) in New Zealand rabbit

Objective: The present study was carried out to evaluate morphometric and histopathological abnormalities during organogenesis in liver, kidney, brain, spinal cord, heart, Lung, digestive tract and spleen in rabbit feti in response to oral administration of Khat prepared from leaves of khat tree ( Catha edulis ). Materials and methods: The current work was carried out with apparently healthy adult New Zealand rabbits (n=27; 3 males and 24 females) weighing 2.5±0.5 Kg. The female rabbits were divided into four equal groups. Three goups (low, medium and high dose groups) were treated with Khat . The groups were given 3 mL, 6 mL and 12 mL extract/Kg bwt once daily from day 8 to 18 of gestation, respectively. The control group was given distilled water only. All females were slaughtered on day 28 of gestation. Visceral organ were subjected for histopathological examinations. Results: Khat was found to be associated with hepatotoxicity and nephrotoxicity in rabbits. The kidney of feti of treated dams showed subcapsular hemorrhages along with mild vacuolar degeneration of some renal tubular epithelium. Glomeruli were atrophied, and moderate degenerative changes were observed in renal tubular epithelium and hemorrhages between renal tubules. The liver of the feti showed vacuolar degeneration, necrotic hepatitis, congestion of central veins and hepatic sinusoids, pyknotic clumped nuclei, hemorrhages, edema with atrophy of some hepatocytes, and hyperplasia of Megakaryocytic cells. The Khat also harmed the brain causing hemorrhage, edema, degenerative changes, swelling and necrotic changes of some nerve cells as well as supporting cells. The spinal cord was affected showing degeneration of nerve fibers in white matter and some neurons in grey matter. The heart of treated feti showed congestion of epicardial blood vessels and diffuse degeneration of heart muscles. Lung and alimentary tract only showed congestion of blood vessels. Conclusion: Prenatal exposure of Khat in rabbit induces harmful effects in defferent visceral organs including liver, kidney, brain, spinal cord, spleen, intestine, heart and lung. http://doi.org/10.5455/javar.2018.e242

Diffusion tensor imaging of brain white matter in rats with ischemia reperfusion injury and its behavioral changes

Objective To investigate the changes of diffusion tensor imaging (DTI) in the cerebral white matter of rats with ischemia-reperfusion injury. Methods Adult SD rats were randomly divided into two groups, sham operation group and model group. The model of ischemia reperfusion injury was made by the Koizumi suture method to occlude the middle cerebral artery. Application of Zea-Longa score was carried out to determine the establishment of modeling, and the modified neurological severity score (mNSS) was used to evaluate the neurological deficit of rats. The Rotarod test instrument was used to observe the motor function of rats by using Rotarod fatigue balance signs, and the DTI sequence scanning observation of brain white matter nerve fiber damage was determined by using Brook 7.0T small animal magnetic resonance imaging system. Track Vis software was used to analyze the distribution of cerebral white matter nerve fibers, and the relative number of nerve fibers in the areas of ROI (region of interest, ROI), sensorimotor areas and striatum were calculated. Results The results showed varying degrees of neurological impairment in rats 2 h after cerebral ischemia reperfusion injury, and the Zea-Longa score and the mNSS score were gradually reduced at the 1 d, 7 d and 14 d after ischemia reperfusion injury. The time of rats retaining on the rotating rod was shortened at the 7 d and 14 d after ischemia reperfusion injury. At the ischemic lateral, nerve fibers decreased significantly, and the number of sensory nerve fiber connections in the sensorimotor areas to striatum was reduced. Nissl staining showed that the cytoplasm of neurons in the sensorimotor cortex and striatum of the ischemic lateral were disappeared and the Nissl bodies were decreased. Conclusions The nerve fibers of sensory motor cortex connecting to striatum were damaged by ischemia reperfusion injury. Key words: Ischemia reperfusion injury; Brain white matter; DTI imaging; Sensorimotor; Striatum

Methodology for computing white matter nerve fiber orientation in human histological slices

BackgroundThe gold standard for mapping nerve fiber orientation in white matter of the human brain is histological analysis through biopsy. Such mappings are a crucial step in validating non-invasive techniques for assessing nerve fiber orientation in the human brain by using diffusion MRI. However, the manual extraction of nerve fiber directions of histological slices is tedious, time consuming, and prone to human error. New methodThe presented semi-automated algorithm first creates a binary-segmented mask of the nerve fibers in the histological image, and then extracts an estimate of average directionality of nerve fibers through a Fourier-domain analysis of the masked image. It also generates an uncertainty level for its estimate of average directionality. Results and comparison with existing methodsThe average orientations of the semi-automatic method were first compared to a qualitative expert opinion based on visual inspection of nerve fibers. A weighted RMS difference between the expert estimate and the algorithmically determined angle (weighted by expert's confidence in his estimate) was 15.4°, dropping to 9.9° when only cases with an expert confidence level of greater than 50% were included. The algorithmically determined angles were then compared with angles extracted using a manual segmentation technique, yielding an RMS difference of 11.2°. ConclusionThe presented semi-automated method is in good agreement with both qualitative and quantitative manual expert-based approaches for estimating directionality of nerve fibers in white matter from images of stained histological slices of the human brain.

Spontaneous white matter lesion in brain of stroke-prone renovascular hypertensive rats: a study from MRI, pathology and behavior.

Hypertension is considered one of the most important controllable risk factors for white matter lesion (WML). Our previous work found that stroke-prone renovascular hypertensive rats (RHRSP) displayed a high rate of WML. This study aimed to investigate the WML in RHRSP from MRI, pathology and behavior. RHRSP model was established by two-kidney, two-clipmethod and kept for 20 weeks. WML was decteted by magnetic resonance imaging (MRI) and loyez staining. Cognition was tested by morris water maze (MWM). Vascular changes were observed by HE staining on brain and carotid sections. Ultrastucture of blood brain barrier (BBB) were observed by transmission electron microscope. Immunofluorescence was used to detect albumin leakage and cell proliferation. T(2)-weighted MRI scans of RHRSP displayed diffuse, confluent white-matter hyperintensities. Pathological examination of the same rat showed marked vacuoles, disappearence of myelin and nerve fibers in white matter, supporting the neuroimaging findings. Spatial learning and memory impairment were observed in RHRSP. The small arteries in brain exhibited fibrinoid necrosis, hyalinosis and vascular remodeling. BBB disruption and plasma albumin leakage into vascular wall was observed in RHRSP. Increased cell proliferation in subventricular zone was seen in RHRSP. RHRSP demonstrated spontaneous WML and cognitive impairment. Hypertensive small vessel lesions and BBB disruption might paly causative factors for the onset and development of WML. The characteristic features of WML in RHRSP suggested it a valid animal model for WML.

Fiber orientation-dependent white matter contrast in gradient echo MRI

Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) and the contrast observed in magnitude and phase images acquired using gradient echo MRI. Understanding the origin of this link is of great interest because it could offer access to a new diagnostic tool for investigating tissue microstructure. Since it has been suggested that myelin is the dominant source of this contrast, creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the NMR signal is an essential step toward fully understanding WM contrast. In this study, we show by comparison of the results of simulations and experiments carried out on human subjects at 7T, that the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic magnetic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T(2) relaxation time and spin density relative to its surroundings, and also undergoes exchange. The accuracy and intrinsic simplicity of the hollow cylinder model provides a versatile framework for future exploitation of the effect of WM microstructure on gradient echo contrast in clinical MRI.

STEREOLOGY OF NEURONAL CONNECTIONS (MYELINATED FIBERS OF WHITE MATTER AND SYNAPSES OF NEOCORTEX) IN HUMAN BRAIN

Unbiased stereological sampling and counting techniques for estimating the total length, total volume and diameter distribution of myelinated nerve fibers in white matter and the total number of synapses in neocortex of human autopsy brains were described. Uniform random sampling of tissues from entire hemisphere was performed. The total volume and total length of myelinated fibers in white matter were estimated from the product of the volume of white matter obtained with the Cavalieri principle and the volume density and length density of myelinated fibers in white matter, respectively. The volume density of myelinated nerve fibers in white a matter was estimated with a point counting method. The length density of myelinated fibers in white matter was estimated from the isotropic, uniform random sections that were ensured by the sector. The diameter of myelinated fibers was derived by measuring the profile diameterperpendicular to its longest axis. The ethanolic phosphotungstic acid staining technique was modified for staining synapses in human autopsy brains. The total number of synapses in each neocortical region was estimated as the product of the volume of each neocortical region and the numerical density of synapses in each region. The numerical density of synapses in each neocortical region was obtained with the disector at the electron microscopical level. The presented methods will be useful for quantitative studies of the changes of myelinated nerve fibers and synapses in various distinct regions of the central nervous system due to development, aging and diseases.

Utility of diffusion tensor imaging in the acute stage of mild to moderate traumatic brain injury for detecting white matter lesions and predicting long-term cognitive function in adults

Traumatic brain injury (TBI) often impairs cognitive function. Diffusion tensor (DT) imaging, a novel modality, permits evaluation of the effects of head trauma on white matter nerve fibers. The objectives of the current study were to investigate where the white matter injury following mild to moderate TBI is specifically located on DT imaging in the acute disease stage and to examine the relationship between the severity of the white matter lesion on DT imaging in the acute stage of TBI and future cognitive function in the chronic disease stage. Twenty adult patients with mild to moderate TBI (Glasgow Coma Scale score between 9 and 15) underwent conventional MR and DT imaging a median of 3.5 days after injury, and 27 matched healthy controls also underwent both imaging modalities. The patients with TBI were further subdivided into 2 groups, that is, mild and more severe TBI groups, based on clinical (mild or moderate TBI), CT (diffuse brain injury [DBI] I or II), or MR imaging (normal or pathological appearance) classification. Fractional anisotropies (FAs) were compared between patients and controls using the region of interest method. Regions of interest were located in 8 different areas including the genu, stem, and splenium of the corpus callosum and the corona radiata (CR), anterior limb of the internal capsule (ALIC), posterior limb of the internal capsule (PLIC), frontal white matter (FWM), and occipital white matter (OWM) of the periventricular white matter. Eleven patients with TBI also underwent neuropsychological testing, which included the Trail Making Test, Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revised, and P300 testing in the chronic disease stage (median 364 days). Region of interest analysis demonstrated significantly lower FA values in the genu, stem, and splenium of the corpus callosum in more severe TBI groups (moderate TBI on clinical classification, DBI II on CT classification, and pathological appearance on MR imaging classification) than in controls. A significant difference was also observed in the FA of the splenium between controls and the mild TBI group of the clinical classification. No significant difference was observed in the FA of the CR, ALIC, PLIC, FWM, and OWM between controls and any of the TBI groups of clinical or imaging classifications. No significant difference was observed in the FA of any regions between mild and more severe TBI groups of the clinical or imaging classifications. Multiple regression analysis showed a statistically significant positive linear relationship between FA in the splenium and total IQ (r = 0.79, p = 0.004). A significant negative linear relationship between FA in the FWM and P300 latency was also observed (r = 0.62, p = 0.04). Fractional anisotropy reductions in the splenium and FWM in the acute stage of mild to moderate TBI may be a useful prognostic factor for long-term cognitive dysfunction.

Neuroprotective Action of Hypothalamic Peptide PRP-1 at Various Time Survivals Following Spinal Cord Hemisection

The purpose of the present study was to evaluate the neuroprotective action of proline-rich peptide-1 (PRP-1) produced by hypothalamic nuclei cells (nuclei paraventricularis and supraopticus) following lateral hemisection of spinal cord (SC). The dynamics of rehabilitative shifts were investigated at various periods of postoperative survival (1-2, 3, and 4 weeks), both with administration of PRP-1 and without it (control). We registered evoked spike flow activity in both interneurons and motoneurons of the same segment of transected and symmetric intact sides of SC and below it on the stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius) and extensor (n. peroneus communis) nerves. In the control group (administration of 0.9% saline as placebo), no significant decrease of post-stimulus activity of neurons was observed on the transected side by the 2nd week. This activity strongly decreased by week 3 postaxotomy, with some increase on the intact side, possibly of compensatory origin. No shifts occurred by the 4th week. Regardless of the period of administration, PRP-1 increased neuronal activity on the transected side, with the same activation levels on both SC sides. These data were confirmed by histochemical investigation. PRP-1 administration, both daily and every other day, for a period of 2-3 weeks led to prevention of scar formation and promotion of the re-growth of white matter nerve fibers in the damaged area. It also resulted in prevention of neuroglial elements degeneration and reduction in gliosis expression in the lesion supporting neuronal survival. Thus, PRP-1 achieved protection against "tissue stress", which was also confirmed by the registration of activity on the level of transection and restoration of the motor activity on the injured side. The obtained data propose the possibility of PRP-1 application in clinical practice for prevention of neurodegeneration of traumatic origin.

A stereological method for estimating the total length and size of myelin fibers in human brain white matter

A practically unbiased stereological method to obtain estimates of the volume and total length of nerve fibers in brain white matter is described. The sampling scheme is designed so that the majority of brain white matter is left intact, thus providing the possibility for resampling and further analysis. Uniform sampling of one complete hemispherical white matter is performed. The volume fraction of nerve fibers in white matter is estimated by point counting. The total length of nerve fibers was estimated from the product of the volume of white matter, obtained with the Cavalieri principle, and the fiber length density, obtained from the isotropic, uniform random sections which were ensured by the isector. The size of nerve fibers was derived by measuring the profile diameter perpendicular to its longest axis. The influence of the postmortem fixation delay on nerve fiber parameters was investigated in one dog and one pig. The criteria for identification of nerve fiber profiles at light microscopy were evaluated using electron microscopy.

Histopathologic and morphometric study of spinal cord lesion in a chronic cord compression model using bone morphogenetic protein in rabbits.

Chronic compressive myelopathy was induced in domestic rabbits by implanting bone morphogenetic protein on the ligamentum flavum of the lumbar spine, and the resulting spinal cord lesion was studied histopathologically. In addition, morphometry of myelinated nerve fibers of the white matter in the pathologic specimens was performed to elucidate the mechanisms of cord injury. No loss of white matter nerve fibers was seen when the cord compression ratio (sagittal diameter/transverse diameter) was > 45%, although 6 months later myelin thinning was present throughout the white matter. When the cord compression ratio was < or = 45%, loss of fibers, particularly of large fibers, was seen in the superficial layer of the white matter, with the nerve fibers remaining after 6 months showing decreased diameters. No motor paresis was evident in any animal. These histologic changes represent the early pathologic condition induced by chronic cord compression.