Single‐ and double‐Diffusion encoding MRI for studying ex vivo apparent axon diameter distribution in spinal cord white matter

2019 ◽  
Vol 32 (12) ◽  
Author(s):  
Debbie Anaby ◽  
Darya Morozov ◽  
Inbar Seroussi ◽  
Simon Hametner ◽  
Nir Sochen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Ex Vivo ◽  
Double Diffusion ◽  
Diameter Distribution ◽  
Axon Diameter

Identification of Severities of Spinal Cord Injury during Acute Phase in Rats by Diffusion Tensor Imaging

2020 ◽  
Author(s):  
Beike Chen ◽  
Qiang Tan ◽  
Weikang Zhao ◽  
Qiming Yang ◽  
Hongyan Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Motor Evoked Potentials ◽  
Ex Vivo ◽  
Female Rats ◽  
Aneurysm Clip ◽  
Cord Injury

Abstract Background: Diffusion tensor imaging (DTI) was an effective method to identify subtle changes to normal‐appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stage. Method: Except for 2 Sprague -Dawley rats died from anesthesia accident, the rest 42 female rats were randomized into 3 groups: control (n=6), moderate group (n=18), and severe group (n=18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae were induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. Results: In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than that of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, reflected in the robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. Conclusions: Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.

scholarly journals Does powder averaging remove dispersion bias in diffusion MRI diameter estimates within real 3D axonal architectures?

2021 ◽  
Author(s):  
Mariam Andersson ◽  
Marco Pizzolato ◽  
Hans Martin Kjer ◽  
Katrine Forum Skodborg ◽  
Henrik Lundell ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Ex Vivo ◽  
Dynamic Properties ◽  
High Signal ◽  
Axon Diameter ◽  
Signal To Noise ◽  
B Values ◽  
Wide Range

Noninvasive estimation of axon diameter with diffusion MRI holds potential to investigate the dynamic properties of the brain network and pathology of neurodegenerative diseases. Recent methods use powder averaging to account for complex white matter architectures, such as fibre crossing regions, but these have not been validated for real axonal geometries. Here, we present 120-313 μm long segmented axons from X-ray nano-holotomography volumes of a splenium and crossing fibre region of a vervet monkey brain. We show that the axons in the complex crossing fibre region, which contains callosal, association, and corticospinal connections, are larger and exhibit a wider distribution than those of the splenium region. To accurately estimate the axon diameter in these regions, therefore, sensitivity to a wide range of diameters is required. We demonstrate how the q-value, b-value, signal-to-noise ratio and the assumed intra-axonal parallel diffusivity influence the range of measurable diameters with powder average approaches. Furthermore, we show how Gaussian distributed noise results in a wider range of measurable diameter at high b-values than with Rician distributed noise, even at high signal-to-noise ratios of 100. The number of gradient directions is also shown to impose a lower bound on measurable diameter. Our results indicate that axon diameter estimation can be performed with only few b-shells, and that additional shells do not improve the accuracy of the estimate. Through Monte Carlo simulations of diffusion, we show that powder averaging techniques succeed in providing accurate estimates of axon diameter across a range of sequence parameters and diffusion times, even in complex white matter architectures. At sufficiently low b-values, the acquisition becomes sensitive to axonal microdispersion and the intra-axonal parallel diffusivity shows time dependency at both in vivo and ex vivo intrinsic diffusivities.

scholarly journals Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

2018 ◽  
Vol 6 ◽  
Author(s):  
Noam Shemesh
Keyword(s):  
Spinal Cord ◽  
Fractional Anisotropy ◽  
Double Diffusion ◽  
Orientation Distribution ◽  
Axon Diameter ◽  
Rat Spinal Cord ◽  
Tissue Microstructure ◽  
Water Fraction ◽  
Path Lengths ◽  
Magnetic Resonance Imaging Mri

Mapping tissue microstructure accurately and noninvasively is one of the frontiers of biomedical imaging. Diffusion Magnetic Resonance Imaging (MRI) is at the forefront of such efforts, as it is capable of reporting on microscopic structures orders of magnitude smaller than the voxel size by probing restricted diffusion. Double Diffusion Encoding (DDE) and Double Oscillating Diffusion Encoding (DODE) in particular, are highly promising for their ability to report on microscopic fractional anisotropy (μFA), a measure of the pore anisotropy in its own eigenframe, irrespective of orientation distribution. However, the underlying correlates of μFA have insofar not been studied. Here, we extract μFA from DDE and DODE measurements at ultrahigh magnetic field of 16.4T with the goal of probing fixed rat spinal cord microstructure. We further endeavor to correlate μFA with Myelin Water Fraction (MWF) derived from multiexponential T2 relaxometry, as well as with literature-based spatially varying axon diameter. In addition, a simple new method is presented for extracting unbiased μFA from three measurements at different b-values. Our findings reveal strong anticorrelations between μFA (derived from DODE) and axon diameter in the distinct spinal cord tracts; a moderate correlation was also observed between μFA derived from DODE and MWF. These findings suggest that axonal membranes strongly modulate μFA, which—owing to its robustness toward orientation dispersion effects—reflects axon diameter much better than its typical FA counterpart. μFA varied when measured via oscillating or blocked gradients, suggesting selective probing of different parallel path lengths and providing insight into how those modulate μFA metrics. Our findings thus shed light into the underlying microstructural correlates of μFA and are promising for future interpretations of this metric in health and disease.

scholarly journals Modelling conduction delays in the corpus callosum using MRI-measured g-ratio

2018 ◽  
Author(s):  
S. Berman ◽  
S. Filo ◽  
A. A. Mezer
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Quantitative Mri ◽  
Biophysical Model ◽  
Diameter Distribution ◽  
Conduction Delay ◽  
Axon Diameter ◽  
Healthy Human ◽  
G Ratio

AbstractConduction of action potentials along myelinated axons is affected by their structural features, such as the axonal g-ratio, the ratio between the inner and outer diameters of the myelin sheath surrounding the axon. The effect of g-ratio variance on conduction properties has been quantitatively evaluated using single-axon models. It has recently become possible to estimate a g-ratio weighted measurement in vivo using quantitative MRI. Nevertheless, it is still unclear whether the variance in the g-ratio in the healthy human brain leads to significant differences in conduction velocity. In this work we tested whether the g-ratio MRI measurement can be used to predict conduction delays in the corpus callosum.We present a novel framework in which the structural properties of fibers (i.e. length and g-ratio, measured using MRI), are incorporated in a biophysical model of axon conduction, to predict conduction delays of long-range white matter fibers. We applied this framework to the corpus callosum, and found conduction delay estimates that are compatible with previously estimated values of conduction delays. We account for the variance in the velocity given the axon diameter distribution in the splenium, mid-body and genu, to further compare the fibers within the corpus callosum.Conduction delays have been suggested to increase with age. Therefore, we investigated whether there are differences in the g-ratio and the fiber length between young and old adults, and whether this leads to a difference in conduction speed and delays. We found small but significant differences between the predicted delays of the two groups in the motor fibers of the corpus callosum. We also found that the motor fibers of the corpus callosum have the fastest conduction estimates. Using the axon diameter distributions, we found that the occipital fibers have the slowest estimations, while the frontal and motor fiber tracts have similar estimates.Our study provides a framework for predicting conduction latencies in vivo. The framework could have major implications for future studies of white matter diseases and large range network computations. Our results highlight the need for improving additional in vivo measurements of white matter microstructure.

Biomechanics of Spinal Cord Injury: A Multimodal Investigation Using Ex Vivo Guinea Pig Spinal Cord White Matter

2008 ◽  
Vol 25 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Hui Ouyang ◽  
Beth Galle ◽  
Jianming Li ◽  
Eric Nauman ◽  
Riyi Shi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Guinea Pig ◽  
Ex Vivo ◽  
Cord Injury

scholarly journals White matter microstructure from nonparametric axon diameter distribution mapping

NeuroImage ◽  
2016 ◽  
Vol 135 ◽  
pp. 333-344 ◽  
Author(s):  
Dan Benjamini ◽  
Michal E. Komlosh ◽  
Lynne A. Holtzclaw ◽  
Uri Nevo ◽  
Peter J. Basser
Keyword(s):  
White Matter ◽  
Diameter Distribution ◽  
Axon Diameter ◽  
White Matter Microstructure ◽  
Distribution Mapping

Critical roles of decompression in functional recovery of ex vivo spinal cord white matter

2009 ◽  
Vol 10 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Hui Ouyang ◽  
Beth Galle ◽  
Jianming Li ◽  
Eric Nauman ◽  
Riyi Shi
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Ex Vivo ◽  
Membrane Damage ◽  
Compound Action Potential ◽  
Axonal Membrane ◽  
Cord Injury ◽  
Decompression Procedure ◽  
Spinal Cord Decompression ◽  
Type Of Injury

Object The correlations between functional deficits, the magnitude of compression, and the role of sustained compression during traumatic spinal cord injury remain largely unknown. Thus, the functional outcome of this type of injury with or without surgical intervention is rather unpredictable. To elucidate how severity and duration of compression affect cord function, the authors have developed a method to study electrophysiological characteristics and axonal membrane damage in white matter from guinea pig spinal cord. Methods Ventral white matter strips isolated from adult guinea pigs were compressed by a compression rod at a level of either 60 or 80% and held briefly, for 30 minutes, or for 60 minutes. In half the experimental groups, a decompression phase consisting of probe withdrawal and 30 minutes of recovery was also applied. For all cord samples, functional response was continuously monitored through compound action potential (CAP) recording. In addition, axonal membrane damage was assessed by a horseradish peroxidase (HRP) exclusion assay. Results After 30 minutes of sustained compression at levels of 60 or 80%, a spinal cord decompression procedure caused a significant CAP recovery, with specimens reaching 97.5 ± 6.84% (p < 0.05) and 56.2 ± 6.14% (p < 0.05) of preinjury amplitude, respectively. After 60 minutes of compression, the amount of CAP recovery following the decompression stage was only 65.5 ± 9.33% for 60% compression (p < 0.05) and 29.8 ± 6.31% for 80% compression (p < 0.05). Unlike the CAP response, HRP uptake did not increase during sustained compression, and the data showed that HRP staining was primarily time dependent. Conclusions The degree of axonal membrane damage is not exacerbated during sustained compression. However, the electrical conductivity of the cord white matter weakens throughout the duration of compression. Therefore, decompression is a viable procedure for preservation of neurological function following compressive injury.

scholarly journals Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice

2021 ◽  
Vol 22 (7) ◽  
pp. 3604
Author(s):  
Nicola Alessio ◽  
Carmela Belardo ◽  
Maria Consiglia Trotta ◽  
Salvatore Paino ◽  
Serena Boccella ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vitamin D ◽  
Chronic Pain ◽  
Vitamin D Deficiency ◽  
Morphological Analysis ◽  
Pain Perception ◽  
Ex Vivo ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects

The bioactive form of vitamin .D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

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