Diffusion tensor imaging and tractwise fractional anisotropy statistics: quantitative analysis in white matter pathology

Background  

Information on anatomical connectivity in the brain by measurements of the diffusion of water in white matter tracts lead to quantification of local tract directionality and integrity.     

Polyunsaturated fatty acids and brain white matter anisotropy in recent-onset schizophrenia: A preliminary study

Brain white matter myelin abnormalities and cell membrane fatty acid abnormalities have been implicated in schizophrenia and other psychiatric disorders. We investigated in young adults with a psychotic disorder (n=12) whether (poly)unsaturated fatty acid concentrations in erythrocyte membranes are related to an MRI measure of brain white matter, which depends on the degree of myelination. A significant correlation was found between total (poly)unsaturated fatty acid concentration and fractional anisotropy of a fronto-temporal white matter tract (r=0.503, P=0.048). Unsaturated fatty acids may be necessary for the myelinating activity of oligodendrocytes or for myelin maintenance. These results warrant further investigation.     

Functional diffusion tensor imaging: measuring task-related fractional anisotropy changes in the human brain along white matter tracts

Background

Functional neural networks in the human brain can be studied from correlations between activated gray matter regions measured with fMRI. However, while providing important information on gray matter activation, no information is gathered on the co-activity along white matter tracts in neural networks.

Methodology/Principal Findings

We report on a functional diffusion tensor imaging (fDTI) method that measures task-related changes in fractional anisotropy (FA) along white matter tracts. We hypothesize that these fractional anisotropy changes relate to morphological changes of glial cells induced by axonal activity although the exact physiological underpinnings of the measured FA changes remain to be elucidated. As expected, these changes are very small as compared to the physiological noise and a reliable detection of the signal change would require a large number of measurements. However, a substantial increase in signal-to-noise ratio was achieved by pooling the signal over the complete fiber tract. Adopting such a tract-based statistics enabled us to measure the signal within a practically feasible time period. Activation in the sensory thalamocortical tract and optic radiation in eight healthy human subjects was found during tactile and visual stimulation, respectively.

Conclusions/Significance

The results of our experiments indicate that these FA changes may serve as a functional contrast mechanism for white matter. This noninvasive fDTI method may provide a new approach to study functional neural networks in the human brain.     

Proteomic studies on the white matter of human brain

Limited information on the protein expression profiles of the different components of mammalian brain is available to date. In the present study, proteomic analysis was performed on 32 white matter samples obtained from 8 different regions of brains of four post mortem cases. Proteins were separated by 2D gel electrophoresis and identified by mass spectrometry. Most of the protein spots (98%) are reproducibly present in all the samples analyzed. A total of 64 different proteins were identified and divided into seven functional groups. These include metabolic proteins (33%), structural proteins (9%), proteins involved in signal transduction (9%), blood proteins (8%), stress related proteins (23%), and proteins involved in the ubiquitin mediated proteolysis (6%). This protein database obtained from the white matter of human brain contributes to deepen our knowledge on the molecular mechanisms that control several pathologies affecting this key component of the brain.     

The influence of the respiratory cycle on the EEG

In order to evaluate the influence of the respiratory cycle on the EEG, we compared the power spectral analysis of the EEG performed by fast Fourier transformation during inspirium and exspirium in 10 healthy subjects. The measurement was performed during spontaneous breathing and then during eupnoe (0.25 Hz), bradypnoe (0.1 Hz) and tachypnoe (0.5 Hz) paced by a metronome. In the course of spontaneous breathing and bradypnoe, there was an increase in the delta power and in the total power in the anterior temporal region during inspirium in comparison with exspirium. The eupnoe was characterized by an inspiratory decrease in the delta power in the parietal region and in the total power in the frontal region. The tachypnoe resulted in a decrease of the beta power in the central region and a decrease of the theta power in the posterior temporal and in the occipital region during inspirium. In comparison of the EEG in eupnoe, bradypnoe and tachypnoe, a decrease of spectral power of all spectral bands was found except for delta during faster breathing frequencies and vice versa with a significant difference which was found mostly between bradypnoe and tachypnoe, less frequently between eupnoe and tachypnoe.     

NMR approach of the periventricular white matter

From a series of 117 neurological patients presenting a pathological periventricular white matter signal on NMR, the authors discuss the differential diagnosis possibilities based on the configuration of the lesions, on their localization in the brain, and on the calculated apparent T2 (T2**) values achieved with the single multi-echos technique.     

Unconfined compression of white matter

The porous properties of brain tissue are important for understanding normal and abnormal cerebrospinal fluid flow in the brain. In this study, a poroviscoelastic model was fitted to the stress relaxation response of white matter in unconfined compression performed under a range of low strain rates. A set of experiments was also performed on the tissue samples using a no-slip boundary condition. Results from these experiments demonstrated that the rheological response of the white matter is primarily governed by the intrinsic viscoelastic properties of the solid phase. The permeability of white matter was found to be of the order of 10(-12) m4/Ns.     

The influence of anisotropy on brain injury prediction

Traumatic Brain Injury (TBI) occurs when a mechanical insult produces damage to the brain and disrupts its normal function. Numerical head models are often used as tools to analyze TBIs and to measure injury based on mechanical parameters. However, the reliability of such models depends on the incorporation of an appropriate level of structural detail and accurate representation of the material behavior. Since recent studies have shown that several brain regions are characterized by a marked anisotropy, constitutive equations should account for the orientation-dependence within the brain. Nevertheless, in most of the current models brain tissue is considered as completely isotropic. To study the influence of the anisotropy on the mechanical response of the brain, a head model that incorporates the orientation of neural fibers is used and compared with a fully isotropic model. A simulation of a concussive impact based on a sport accident illustrates that significantly lowered strains in the axonal direction as well as increased maximum principal strains are detected for anisotropic regions of the brain. Thus, the orientation-dependence strongly affects the response of the brain tissue. When anisotropy of the whole brain is taken into account, deformation spreads out and white matter is particularly affected. The introduction of local axonal orientations and fiber distribution into the material model is crucial to reliably address the strains occurring during an impact and should be considered in numerical head models for potentially more accurate predictions of brain injury.     

Modeling the influence of cyclodextrins on oral absorption of low solubility drugs: II. Experimental validation

A model was developed for predicting the influence of cyclodextrins (CDs) delivered as a physical mixture with drug on oral absorption. CDs are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. The purpose of this work is to compare the simulation predictions with in vitro as well as in vivo experimental results to test the model's ability to capture the influence of CD on key processes in the gastrointestinal (GI) tract environment. Dissolution and absorption kinetics of low solubility drugs (Naproxen and Nifedipine) were tested in the presence and absence of CD in a simulated gastrointestinal environment. Model predictions were also compared with in vivo experimental results (Glibenclamide and Carbamazepine) from the literature to demonstrate the model's ability to predict oral bioavailability. Comparisons of simulation and experimental results indicate that a model incorporating the influence of CD (delivered as a physical mixture) on dissolution kinetics and binding of neutral drug can predict trends in the influence of CD on bioavailability. Overall, a minimal effect of CD dosed as a physical mixture was observed and predicted. Modeling may aid in enabling rational design of CD containing formulations. Biotechnol. Bioeng. 2010; 105: 421–430. © 2009 Wiley Periodicals, Inc.     

Prestimulus EEG influence on late ERP components

Ten healthy volunteers were submitted to an auditory oddball event related potentials (ERP) paradigm. Single trial 500 ms poststimulus ERPs (Pz, Cz, Fz--linked earlobes) along with the correspondent 1000 ms prestimulus EEG (O1-Cz) were stored. EEG epochs were submitted to spectral analysis and a slow wave index (SWI = delta + theta/total) was computed. Three selective ERP averages corresponding to low, medium and high SWI were computed. N2 latency was longer and P3a amplitude was lower in high SWI averages as compared to low SWI averages.     

Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations

The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction.     

Q-ball imaging of macaque white matter architecture

Diffusion-weighted magnetic resonance imaging holds substantial promise as a technique for non-invasive imaging of white matter (WM) axonal projections. For diffusion imaging to be capable of providing new insight into the connectional neuroanatomy of the human brain, it will be necessary to histologically validate the technique against established tracer methods such as horseradish peroxidase and biocytin histochemistry. The macaque monkey provides an ideal model for histological validation of the diffusion imaging method due to the phylogenetic proximity between humans and macaques, the gyrencephalic structure of the macaque cortex, the large body of knowledge on the neuroanatomic connectivity of the macaque brain and the ability to use comparable magnetic resonance acquisition protocols in both species. Recently, it has been shown that high angular resolution diffusion imaging (HARDI) can resolve multiple axon orientations within an individual imaging voxel in human WM. This capability promises to boost the accuracy of tract reconstructions from diffusion imaging. If the macaque is to serve as a model for histological validation of the diffusion tractography method, it will be necessary to show that HARDI can also resolve intravoxel architecture in macaque WM. The present study therefore sought to test whether the technique can resolve intravoxel structure in macaque WM. Using a HARDI method called q-ball imaging (QBI) it was possible to resolve composite intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel structure in, for example, the dorsolateral convexity, the pontine decussation, the pulvinar and temporal subcortical WM. The paper concludes by reviewing remaining challenges for the diffusion tractography project.     

Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study

Abnormalities of frontal white matter (WM) have been found in some children with ADHD. The purpose of this study was to explore the changes in WM in child patients with ADHD by DTI, which detects changes in WM microstructure based on properties of diffusion. We also expect to investigate the relationship between the changes in WM and executive function in child patients with ADHD. DTI was performed on 24 patients with ADHD and 20 healthy controls. A series of neuropsychological tests and a structural interview were conducted to assess the cognitive functions and clinical data of the ADHD patients and controls. Firstly, child patients with ADHD have higher fractional anisotropy (FA) values in WM in the right frontal region. Secondly, FA in right frontal WM is positively correlated with scores in the Stroop test. CONCLUSIONS: Increased FA of right frontal WM implies a higher degree of myelination and lower degree of neural branching in WM, contributing to the neurological deficits of ADHD.     

The influence of model parameters on model validation

The study examined the sensitivity of two musculoskeletal models to the parameters describing each model. Two different models were examined: a phenomenological model of human jumping with parameters based on live subject data, and the second a model of the First Dorsal Interosseous with parameters based on cadaveric measurements. Both models were sensitive to the model parameters, with the use of mean group data not producing model outputs reflective of either the performance of any group member or the mean group performance. These results highlight the value of subject specific model parameters, and the problems associated with model validation.