9,618 research outputs found
Biophysically motivated efficient estimation of the spatially isotropic R*2 component from a single gradientârecalled echo measurement
Purpose
To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientationâdependent part of R*2 using a single gradientârecalled echo (GRE) measurement.
Methods
The proposed method utilized a temporal secondâorder approximation of the hollowâcylinderâfiber model, in which the parameter describing the linear signal decay corresponded to the orientationâindependent part of R*2. The estimated parameters were compared to the classical, monoâexponential decay model for R*2 in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R*2, it was compared to the established phenomenological method for separating R*2 into orientationâdependent and âindependent parts.
Results
Using the phenomenological method on the classical signal model, the wellâknown separation of R*2 into orientationâdependent and âindependent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed.
Conclusions
Since the proposed secondâorder model features orientationâdependent and âindependent components at distinct temporal orders, it can be used to remove the orientation dependence of R*2 using only a single GRE measurement
Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging
The g-ratio, quantifying the comparative thickness of the myelin sheath
encasing an axon, is a geometrical invariant that has high functional relevance
because of its importance in determining neuronal conduction velocity. Advances
in MRI data acquisition and signal modelling have put in vivo mapping of the
g-ratio, across the entire white matter, within our reach. This capacity would
greatly increase our knowledge of the nervous system: how it functions, and how
it is impacted by disease. This is the second review on the topic of g-ratio
mapping using MRI. As such, it summarizes the most recent developments in the
field, while also providing methodological background pertinent to aggregate
g-ratio weighted mapping, and discussing pitfalls associated with these
approaches. Using simulations based on recently published data, this review
demonstrates the relevance of the calibration step for three myelin-markers
(macromolecular tissue volume, myelin water fraction, and bound pool fraction).
It highlights the need to estimate both the slope and offset of the
relationship between these MRI-based markers and the true myelin volume
fraction if we are really to achieve the goal of precise, high sensitivity
g-ratio mapping in vivo. Other challenges discussed in this review further
evidence the need for gold standard measurements of human brain tissue from ex
vivo histology. We conclude that the quest to find the most appropriate MRI
biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of
many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience
Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest
Editor
Axon diameters and myelin content modulate microscopic fractional anisotropy at short diffusion times in fixed rat spinal cord
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 ({\mu}FA), a measure of the pore
anisotropy in its own eigenframe, irrespective of orientation distribution.
However, the underlying correlates of {\mu}FA have insofar not been studied.
Here, we extract {\mu}FA from DDE and DODE measurements at ultrahigh magnetic
field of 16.4T in the aim to probe fixed rat spinal cord microstructure. We
further endeavor to correlate {\mu}FA with Myelin Water Fraction (MWF) derived
from multiexponential T2 relaxometry, as well as with literature-based
spatially varying axonal diameters. In addition, a simple new method is
presented for extracting unbiased {\mu}FA from three measurements at different
b-values. Our findings reveal strong anticorrelations between {\mu}FA (derived
from DODE) and axon diameter in the distinct spinal cord tracts; a moderate
correlation was also observed between {\mu}FA derived from DODE and MWF. These
findings suggest that axonal membranes strongly modulate {\mu}FA, which - owing
to its robustness towards orientation dispersion effects - reflects axon
diameter much better than its typical FA counterpart. The {\mu}FA exhibited
modulations when measured via oscillating or blocked gradients, suggesting
selective probing of different parallel path lengths and providing insight into
how those modulate {\mu}FA metrics. Our findings thus shed light into the
underlying microstructural correlates of {\mu}FA and are (...
Anomalous transport in the crowded world of biological cells
A ubiquitous observation in cell biology is that diffusion of macromolecules
and organelles is anomalous, and a description simply based on the conventional
diffusion equation with diffusion constants measured in dilute solution fails.
This is commonly attributed to macromolecular crowding in the interior of cells
and in cellular membranes, summarising their densely packed and heterogeneous
structures. The most familiar phenomenon is a power-law increase of the MSD,
but there are other manifestations like strongly reduced and time-dependent
diffusion coefficients, persistent correlations, non-gaussian distributions of
the displacements, heterogeneous diffusion, and immobile particles. After a
general introduction to the statistical description of slow, anomalous
transport, we summarise some widely used theoretical models: gaussian models
like FBM and Langevin equations for visco-elastic media, the CTRW model, and
the Lorentz model describing obstructed transport in a heterogeneous
environment. Emphasis is put on the spatio-temporal properties of the transport
in terms of 2-point correlation functions, dynamic scaling behaviour, and how
the models are distinguished by their propagators even for identical MSDs.
Then, we review the theory underlying common experimental techniques in the
presence of anomalous transport: single-particle tracking, FCS, and FRAP. We
report on the large body of recent experimental evidence for anomalous
transport in crowded biological media: in cyto- and nucleoplasm as well as in
cellular membranes, complemented by in vitro experiments where model systems
mimic physiological crowding conditions. Finally, computer simulations play an
important role in testing the theoretical models and corroborating the
experimental findings. The review is completed by a synthesis of the
theoretical and experimental progress identifying open questions for future
investigation.Comment: review article, to appear in Rep. Prog. Phy
Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI
We develop a general analytical and numerical framework for estimating intra-
and extra-neurite water fractions and diffusion coefficients, as well as
neurite orientational dispersion, in each imaging voxel. By employing a set of
rotational invariants and their expansion in the powers of diffusion weighting,
we analytically uncover the nontrivial topology of the parameter estimation
landscape, showing that multiple branches of parameters describe the
measurement almost equally well, with only one of them corresponding to the
biophysical reality. A comprehensive acquisition shows that the branch choice
varies across the brain. Our framework reveals hidden degeneracies in MRI
parameter estimation for neuronal tissue, provides microstructural and
orientational maps in the whole brain without constraints or priors, and
connects modern biophysical modeling with clinical MRI.Comment: 25 pages, 12 figures, elsarticle two-colum
Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.
Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described âmidbrain shrinkage.â Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinsonâs and Alzheimerâs diseases
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