12,968 research outputs found
Multi-compartment microscopic diffusion imaging
This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay
Ranking diffusion-MRI models with in-vivo human brain data
Diffusion MRI microstructure imaging provides a unique non-invasive probe into the microstructure of biological tissue. Its analysis relies on mathematical models relating microscopic tissue features to the MR signal. This work aims to determine which compartment models of diffusion MRI are best at describing the signal from in-vivo brain white matter. Recent work shows that three compartment models, including restricted intra-axonal, glial compartments and hindered extra-cellular diffusion, explain best multi b-value data sets from fixed rat brain tissue. Here, we perform a similar experiment using in-vivo human data. We compare one, two and three compartment models, ranking them with standard model selection criteria. Results show that, as with fixed tissue, three compartment models explain the data best, although simpler models emerge for the in-vivo data. We also find that splitting the scanning into shorter sessions has little effect on the models fitting and that the results are reproducible. The full ranking assists the choice of model and imaging protocol for future microstructure imaging applications in the brain
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
Characterization of multiple sclerosis lesions with distinct clinical correlates through quantitative diffusion MRI
Diffusion magnetic resonance imaging can reveal quantitative information about the tissue changes in multiple sclerosis. The recently developed multi-compartment spherical mean technique can map different microscopic properties based only on local diffusion signals, and it may provide specific information on the underlying microstructural modifications that arise in multiple sclerosis. Given that the lesions in multiple sclerosis may reflect different degrees of damage, we hypothesized that quantitative diffusion maps may help characterize the severity of lesions "in vivo" and correlate these to an individual's clinical profile. We evaluated this in a cohort of 59 multiple sclerosis patients (62% female, mean age 44.7Â years), for whom demographic and disease information was obtained, and who underwent a comprehensive physical and cognitive evaluation. The magnetic resonance imaging protocol included conventional sequences to define focal lesions, and multi-shell diffusion imaging was used with b-values of 1000, 2000 and 3000Â s/mm2 in 180 encoding directions. Quantitative diffusion properties on a macro- and micro-scale were used to discriminate distinct types of lesions through a k-means clustering algorithm, and the number and volume of those lesion types were correlated with parameters of the disease. The combination of diffusion tensor imaging metrics (fractional anisotropy and radial diffusivity) and multi-compartment spherical mean technique values (microscopic fractional anisotropy and intra-neurite volume fraction) differentiated two type of lesions, with a prediction strength of 0.931. The B-type lesions had larger diffusion changes compared to the A-type lesions, irrespective of their location (PÂ <Â 0.001). The number of A and B type lesions was similar, although in juxtacortical areas B-type lesions predominated (60%, PÂ <Â 0.001). Also, the percentage of B-type lesion volume was higher (64%, PÂ <Â 0.001), indicating that these lesions were larger. The number and volume of B-type lesions was related to the severity of disease evolution, clinical disability and cognitive decline (PÂ =Â 0.004, Bonferroni correction). Specifically, more and larger B-type lesions were correlated with a worse Multiple Sclerosis Severity Score, cerebellar function and cognitive performance. Thus, by combining several microscopic and macroscopic diffusion properties, the severity of damage within focal lesions can be characterized, further contributing to our understanding of the mechanisms that drive disease evolution. Accordingly, the classification of lesion types has the potential to permit more specific and better-targeted treatment of patients with multiple sclerosis
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 (...
Effects of nongaussian diffusion on "isotropic diffusion measurements'': an ex-vivo microimaging and simulation study
Designing novel diffusion-weighted pulse sequences to probe tissue
microstructure beyond the conventional Stejskal-Tanner family is currently of
broad interest. One such technique, multidimensional diffusion MRI, has been
recently proposed to afford model-free decomposition of diffusion signal
kurtosis into terms originating from either ensemble variance of isotropic
diffusivity or microscopic diffusion anisotropy. This ability rests on the
assumption that diffusion can be described as a sum of multiple Gaussian
compartments, but this is often not strictly fulfilled. The effects of
nongaussian diffusion on single shot isotropic diffusion sequences were first
considered in detail by de Swiet and Mitra in 1996. They showed theoretically
that anisotropic compartments lead to anisotropic time dependence of the
diffusion tensors, which causes the measured isotropic diffusivity to depend on
gradient frame orientation. Here we show how such deviations from the multiple
Gaussian compartments assumption conflates orientation dispersion with ensemble
variance in isotropic diffusivity. Second, we consider additional contributions
to the apparent variance in isotropic diffusivity arising due to
intracompartmental kurtosis. These will likewise depend on gradient frame
orientation. We illustrate the potential importance of these confounds with
analytical expressions, numerical simulations in simple model geometries, and
microimaging experiments in fixed spinal cord using isotropic diffusion
encoding waveforms with 7.5 ms duration and 3000 mT/m maximum amplitude.Comment: 26 pages, 9 figures. Appearing in J. Magn. Reso
Neurite imaging reveals microstructural variations in human cerebral cortical gray matter
We present distinct patterns of neurite distribution in the human cerebral cortex using diffusion magnetic resonance imaging (MRI). We analyzed both high-resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects from the Human Connectome Project. Neurite distributions were evaluated using the neurite orientation dispersion and density imaging (NODDI) model, optimized for gray matter, and mapped onto the cortical surface using a method weighted towards the cortical mid-thickness to reduce partial volume effects. The estimated neurite density was high in both somatosensory and motor areas, early visual and auditory areas, and middle temporal area (MT), showing a strikingly similar distribution to myelin maps estimated from the T1w/T2w ratio. The estimated neurite orientation dispersion was particularly high in early sensory areas, which are known for dense tangential fibers and are classified as granular cortex by classical anatomists. Spatial gradients of these cortical neurite properties revealed transitions that colocalize with some areal boundaries in a recent multi-modal parcellation of the human cerebral cortex, providing mutually supportive evidence. Our findings indicate that analyzing the cortical gray matter neurite morphology using diffusion MRI and NODDI provides valuable information regarding cortical microstructure that is related to but complementary to myeloarchitecture
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