Altered thalamocortical tract trajectory growth with undisrupted thalamic parcellation pattern in human lissencephaly brain at mid-gestational stage.

Proper topographically organized neural connections between the thalamus and the cerebral cortex are mandatory for thalamus function. Thalamocortical (TC) fiber growth begins during the embryonic period and completes by the third trimester of gestation, so that human neonates at birth have a thalamus with a near-facsimile of adult functional parcellation. Whether congenital neocortical anomaly (e.g., lissencephaly) affects TC connection in humans is unknown. Here, via diffusion MRI fiber-tractography analysis of long-term formalin-fixed postmortem fetal brain diagnosed as lissencephaly in comparison with an age-matched normal one, we found similar topological patterns of thalamic subregions and of internal capsule parcellated by TC fibers. However, lissencephaly fetal brain showed white matter structural changes, including fewer/less organized TC fibers and optic radiations, and much less cortical plate invasion by TC fibers - particularly around the shallow central sulcus. Diffusion MRI fiber tractography of normal fetal brains at 15, 23, and 26 gestational weeks (GW) revealed dynamic volumetric change of each parcellated thalamic subregion, suggesting coupled developmental progress of the thalamus with the corresponding cortex. Moreover, from GW23 and GW26 normal fetal brains, TC endings in the cortical plate could be delineated to reflect cumulative progressive TC invasion of cortical plate. By contrast, lissencephaly brain showed a dramatic decrease in TC invasion of the cortical plate. Our study thus shows the feasibility of diffusion MRI fiber tractography in postmortem long-term formalin-fixed fetal brains to disclose the developmental progress of TC tracts coordinating with thalamic and neocortical growth both in normal and lissencephaly fetal brains at mid-gestational stage.

White matter pathology in alzheimer's transgenic mice with chronic exposure to low-level ambient fine particulate matter.

BACKGROUND: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. RESULTS: 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 µg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. CONCLUSIONS: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Dedicated diffusion phantoms for the investigation of free water elimination and mapping: insights into the influence of T2 relaxation properties.

Conventional diffusion-weighted (DW) MRI suffers from free water contamination due to the finite voxel size. The most common case of free water contamination occurs with cerebrospinal fluid (CSF) in voxels located at the CSF-tissue interface, such as at the ventricles in the human brain. Another case refers to intra-tissue free water as in vasogenic oedema. In order to avoid the bias in diffusion metrics, several multi-compartment methods have been introduced, which explicitly model the presence of a free water compartment. However, fitting multi-compartment models in DW MRI represents a well known ill conditioned problem. Although during the last decade great effort has been devoted to mitigating this estimation problem, the research field remains active. The aim of this work is to introduce the design, characterise the NMR properties and demonstrate the use of two dedicated anisotropic diffusion fibre phantoms, useful for the study of free water elimination (FWE) and mapping models. In particular, we investigate the recently proposed FWE diffusion tensor imaging approach, which takes explicit account of differences in the transverse relaxation times between the free water and tissue compartments.

Effects of signal averaging, gradient encoding scheme, and spatial resolution on diffusion kurtosis imaging: An empirical study using 7T MRI.

BACKGROUND: Although diffusion gradient directions and b-values have been optimized for diffusion kurtosis imaging (DKI), little is known about the effect of signal averaging on DKI reliability. PURPOSE: To evaluate how signal averaging influences the reliability of DKI indices using two gradient encoding schemes with three spatial resolutions. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen naïve Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: DKI was performed at 7T using two schemes (30 directions with three b-values [30d-3b] and six directions with 15 b-values [6d-15b]), three resolutions, and eight repetitions. ASSESSMENT: DKI reliability was assessed using voxelwise relative error (σ) and test-retest error of fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) within gray matter (GM) and white matter (WM). The number of excitations (NEX) was optimized by considering DKI reliability. The influence of the partial volume effect (PVE) was also assessed. STATISTICAL TEST: One-way analysis of variance. RESULTS: The 30d-3b scheme, compared with the 6d-15b scheme, exhibited apparently smaller σFA and σMK (eg, at NEX 1, in GM, for three resolutions, σFA : 19.9-38.2% vs. 34.2-61.4%, σMK : 6.9-11.4% vs. 14.1-15.4%) and similar σMD (all differences between two schemes <1.6%). The optimal NEX was determined as 2 for enabling a reliable measurement of DKI-derived indices. The PVE at the lowest resolution apparently increased σFA for both schemes (19.9% for 30d-3b and 34.2% for 6d-15b) and σMK for the 6d-15b scheme (14.7%) in GM, and exerted lower effects on MK values for the 30d-3b scheme (P > 0.05). DATA CONCLUSION: A higher number of diffusion directions would benefit FA and MK estimation. A higher spatial resolution helps to reduce PVE. By using the 30d-3b scheme, MK is considered a robust index to reflect microstructural changes in GM and WM. We propose a systematic approach to determine the optimal DKI protocols for appropriate preclinical settings. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1593-1603.

Chronic pulmonary exposure to traffic-related fine particulate matter causes brain impairment in adult rats.

BACKGROUND: Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 µm (PM1), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats. RESULTS: The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) µg/m3 of PM1 during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM1 exposure. A short-term memory deficiency occurred with 3 months of exposure to PM1 as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM1 increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM1 exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM1 exposure. CONCLUSIONS: Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.

Observation of the rose petal effect over single- and dual-scale roughness surfaces.

Rose petals exhibit superhydrophobicity with strong adhesion to pin water drops, known as the 'petal effect.' It is generally believed that the petal effect is attributed to dual-scale roughness, that is, the surface possesses both a nanostructure and a microstructure (Feng et al 2008 Langmuir 24 4114). In this study, we demonstrate that the dual-scale roughness is not a necessary condition for a surface of the petal effect. A surface of single-scale roughness, either at the nanoscale or the microscale alone, within a certain roughness region may also exhibit the petal effect. The surface roughness plays the essential role on the wetting behavior and governs the contact angle in the Wenzel or Cassie state, as well as the contact angle hysteresis. A water drop on the surface of the petal effect under the condition of the advancing and receding contact angle would fall into, respectively, the Cassie and Wenzel state, which leads to a contact angle hysteresis large enough to pin the water drop. On both single and dual textured hydrophobic surfaces, a sequence of wetting transitions: Wenzel state → petal state (sticky superhydrophobic state) → lotus state (slippery superhydrophobic state) is consistently observed by simply increasing the surface roughness.

White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma.

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day "0") or repeated mild (1.5 atm on days "0" and "2") traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1-9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.

Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s-/-) mouse. The Blm-s-/- mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s-/- mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s-/- mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s-/- DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression.

Fabrication of sticky and slippery superhydrophobic surfaces via spin-coating silica nanoparticles onto flat/patterned substrates.

Silica nanoparticles were spin-coated onto a flat/patterned (regular pillar-like) substrate to enhance the surface roughness. The surface was further modified by a self-assembled fluorosilanated monolayer. The advancing/receding contact angle and sliding angle measurements were performed to determine the wetting behavior of a water droplet on the surface. It is interesting to find that a transition from a Wenzel surface to a sticky superhydrophobic surface is observed due to the spin-coating silica nanoparticles. A slippery superhydrophobic surface can be further obtained after secondary spin-coating with silica nanoparticles to generate a multi-scale roughness structure. The prepared superhydrophobic substrates should be robust for practical applications. The adhesion between the substrate and nanoparticles is also examined and discussed.

Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.

Diffusion orientation transform revisited.

Diffusion orientation transform (DOT) is a powerful imaging technique that allows the reconstruction of the microgeometry of fibrous tissues based on diffusion MRI data. The three main error sources involving this methodology are the finite sampling of the q-space, the practical truncation of the series of spherical harmonics and the use of a mono-exponential model for the attenuation of the measured signal. In this work, a detailed mathematical description that provides an extension to the DOT methodology is presented. In particular, the limitations implied by the use of measurements with a finite support in q-space are investigated and clarified as well as the impact of the harmonic series truncation. Near- and far-field analytical patterns for the diffusion propagator are examined. The near-field pattern makes available the direct computation of the probability of return to the origin. The far-field pattern allows probing the limitations of the mono-exponential model, which suggests the existence of a limit of validity for DOT. In the regimen from moderate to large displacement lengths the isosurfaces of the diffusion propagator reveal aberrations in form of artifactual peaks. Finally, the major contribution of this work is the derivation of analytical equations that facilitate the accurate reconstruction of some orientational distribution functions (ODFs) and skewness ODFs that are relatively immune to these artifacts. The new formalism was tested using synthetic and real data from a phantom of intersecting capillaries. The results support the hypothesis that the revisited DOT methodology could enhance the estimation of the microgeometry of fiber tissues.

The effect of finite diffusion gradient pulse duration on fibre orientation estimation in diffusion MRI.

An essential step for fibre-tracking is the accurate estimation of neuronal fibre orientations within each imaging voxel, and a number of methods have been proposed to reconstruct the orientation distribution function based on sampling three-dimensional q-space. In the q-space formalism, very short (infinitesimal) gradient pulses are the basic requirement to obtain the true spin displacement probability density function. On current clinical MR systems however, the diffusion gradient pulse duration (delta) is inevitably finite due to the limit on the achievable gradient intensity. The failure to satisfy the short gradient pulse (SGP) requirement has been a recurrent criticism for fibre orientation estimation based on the q-space approach. In this study, the influence of a finite delta on the DW signal measured as a function of gradient direction is described theoretically and demonstrated through simulations and experimental models. Our results suggest that the current practice of using long delta for DW imaging on human clinical MR scanners, which is enforced by hardware limitations, might in fact be beneficial for estimating fibre orientations. For a given b-value, the prolongation of delta is advantageous for estimating fibre orientations for two reasons: first, it leads to a boost in DW signal in the transverse plane of the fibre. Second, it stretches out the shape of the measured diffusion profile, which improves the contrast between DW orientations. This is especially beneficial for resolving crossing fibres, as this contrast is essential to discriminate between different fibre directions.

Self-pinning of silica suspension droplets on hydrophobic surfaces.

HYPOTHESIS: Self-pinning induced by the aggregation of particles at the edge of a pinned drop is a pre-requisite for the coffee ring formation. The edge (three-phase contact line) of a suspension drop on a hydrophobic surface would depin and shrink in the early stage of evaporation process. It is plausible to conjecture that the self-pinning of silica suspension drops depends on the particle size and surface property. EXPERIMENTS: Two substrate materials, the alkylsilane coated surfaces and the polydimethylsiloxane surfaces, and three different sizes of silica particles are used to explore the criterion of self-pinning of silica suspension drops on these hydrophobic surfaces. The evaporation process of droplets is recorded and further analyzed. FINDINGS: The pinning concentration of silica suspensions of a fixed size linearly depends on the receding contact angle of the surface, irrelevant to the substrate material and initial particle concentration. The pinning concentration decreases along with an increase in particle size. In addition, the pinning concentrations of bi-dispersed silica (e.g. 400 + 1000 nm) suspensions have an excellent agreement with that of larger size (1000 nm) particle system. That implies that the larger particle dominates the system of bi-dispersed silica suspensions to initiate the self-pinning, further verified by SEM images.

Probabilistic topography of human corpus callosum using cytoarchitectural parcellation and high angular resolution diffusion imaging tractography.

The function of the corpus callosum (CC) is to distribute perceptual, motor, cognitive, learned, and voluntary information between the two hemispheres of the brain. Accurate parcellation of the CC according to fiber composition and fiber connection is of upmost important. In this work, population-based probabilistic connection topographies of the CC, in the standard Montreal Neurological Institute (MNI) space, are estimated by incorporating anatomical cytoarchitectural parcellation with high angular resolution diffusion imaging (HARDI) tractography. First, callosal fibers are extracted using multiple fiber assignment by continuous tracking algorithm based on q-ball imaging (QBI), on 12 healthy and young subjects. Then, the fiber tracts are aligned in the standard MNI coordinate system based on a tract-based transformation scheme. Next, twenty-eight Brodmann's areas on the surface of cortical cortex are registered to the MNI space to parcellate the aligned callosal fibers. Finally, the population-based topological subdivisions of the midsagittal CC to each cortical target are then mapped. And the resulting subdivisions of the CC that connect to the frontal and somatosensory associated cortex are also showed. To our knowledge, it is the first topographic subdivisions of the CC done using HARDI tractography and cytoarchitectonic information. In conclusion, this sophisticated topography of the CC may serve as a landmark to further understand the correlations between the CC, brain intercommunication, and functional cytoarchitectures.

Preparation of superhydrophobic surfaces of hierarchical structure of hybrid from nanoparticles and regular pillar-like pattern.

The hierarchical structure silica surface of inlaying silica nanoparticles along a regular pillar-like pattern is fabricated by embossing silica sol-gel precursor mixed with silica nanoparticles on glass substrates with an elastomeric mold. The substrate is further modified by a self-assembled fluorosilanated monolayer to reduce its surface energy. The advancing/receding contact angle measurements are performed to demonstrate that a water droplet on these surfaces can exhibit a transition from the Wenzel state to the Cassie state due to the addition of silica nanoparticles to enhance its surface roughness.

Development, integration and use of an ultra-high-strength gradient system on a human-size 3 T magnet for small animal MRI.

This study aims to integrate an ultra-high-strength gradient coil system on a clinical 3 T magnet and demonstrate its preclinical imaging capabilities. Dedicated phantoms were used to qualitatively and quantitatively assess the performance of the gradient system. Advanced MR imaging sequences, including diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), were implemented and executed on an ex vivo specimen as well as in vivo rats. The DTI and QSM results on the phantom agreed well with those in the literature. Furthermore, studies on ex vivo specimens have demonstrated the applicability of DTI and QSM on our system to probe microstructural changes in a mild traumatic brain injury rat model. The feasibility of in vivo rat DTI was also demonstrated. We showed that the inserted ultra-high-strength gradient coil was successfully integrated on a clinically used magnet. After careful tuning and calibration, we verified the accuracy and quantitative preclinical imaging capability of the integrated system in phantom and in vivo rat brain experiments. This study can be essential to establish dedicated animal MRI platform on clinical MRI scanners and facilitate translational studies at clinical settings.

Resolving crossing fibres using constrained spherical deconvolution: validation using diffusion-weighted imaging phantom data.

Diffusion-weighted imaging can potentially be used to infer the connectivity of the human brain in vivo using fibre-tracking techniques, and is therefore of great interest to neuroscientists and clinicians. A key requirement for fibre tracking is the accurate estimation of white matter fibre orientations within each imaging voxel. The diffusion tensor model, which is widely used for this purpose, has been shown to be inadequate in crossing fibre regions. A number of approaches have recently been proposed to address this issue, based on high angular resolution diffusion-weighted imaging (HARDI) data. In this study, an experimental model of crossing fibres, consisting of water-filled plastic capillaries, is used to thoroughly assess three such techniques: constrained spherical deconvolution (CSD), super-resolved CSD (super-CSD) and Q-ball imaging (QBI). HARDI data were acquired over a range of crossing angles and b-values, from which fibre orientations were computed using each technique. All techniques were capable of resolving the two fibre populations down to a crossing angle of 45 degrees , and down to 30 degrees for super-CSD. A bias was observed in the fibre orientations estimated by QBI for crossing angles other than 90 degrees, consistent with previous simulation results. Finally, for a 45 degrees crossing, the minimum b-value required to resolve the fibre orientations was 4000 s/mm(2) for QBI, 2000 s/mm(2) for CSD, and 1000 s/mm(2) for super-CSD. The quality of estimation of fibre orientations may profoundly affect fibre tracking attempts, and the results presented provide important additional information regarding performance characteristics of well-known methods.

Evaluation of the accuracy and angular resolution of q-ball imaging.

Q-ball imaging (QBI) has been proposed for the mapping of multiple intravoxel fiber structures using the Funk-Radon transform on high angular resolution diffusion images (HARDI). However, the accuracy and the angular resolution of QBI to define fiber orientations and its dependence on diffusion imaging parameters remain unclear. The phantom models, made up of sheets of parallel capillaries filled with water, were designed to evaluate the accuracy and the angular resolution of QBI at different |q| values. With an inner diameter of 20 mum and an outer diameter of 90 mum, the capillaries afforded a restrictive environment compared with the diffusion measurement scale. Further, the angular resolutions of QBI at various |q| value were also quantified on the corpus callosum in the human brain. The full width at half maximum (FWHM) of the main lobe of normalized orientation distribution function (nODF) was calculated and adopted to quantify the angular resolution of QBI. With the phantom model, a higher |q| value resulted in worse accuracy but better angular resolution for QBI. The same trend where a higher |q| value yielded a better angular resolution was also observed in the human study. Upon comparison of QBI with T2WI, QBI with |q|=277 cm(-1) (b=3000 s/mm(2)) was found to be insufficient to differentiate capillaries crossing at 45 degrees . However, when encoding with |q|=320, 358, and 392 cm(-1) (b=4000, 5000, and 6000 s/mm(2)), the deviation angles between the primary ODF and the 45 degrees phantoms were -4.91 degrees +/-2.72 degrees , -1.37 degrees +/-2.32 degrees , and -0.69 degrees +/-1.54 degrees with adequate signal-to-noise ratio (SNR). These results were consistent with the FWHM-nODF, which showed that a |q| value of 320 cm(-1) was the threshold to resolve capillaries intersecting at 45 degrees . Additionally, it was demonstrated in both the phantom model and the human brain that QBI encoding with lower |q| values may result in underestimation of the orientations of the crossing fibers. In conclusion, QBI was found to accurately resolve crossing fiber orientations and was highly dependent on the selected |q| value.

A multiple streamline approach to high angular resolution diffusion tractography.

Diffusion-weighted magnetic resonance imaging has the ability to map neuronal architecture by estimating the 3D diffusion displacement within fibrous brain structures. This approach has non-invasively been demonstrated in the human brain with diffusion tensor tractography. Despite its valuable application in neuroscience and clinical studies however, it faces an inherent limit in mapping fiber tracts through areas with intervoxel incoherence. Recent advances in high angular resolution diffusion imaging have surpassed this limit and have the ability to resolve the complex fiber intercrossing within each MR voxel. To connect the fiber tracts from a multi-fiber system, this study proposed a modified fiber assignment using the continuous tracking (MFACT) algorithm and a tracking browser to propagate tracts along complex diffusion profiles. The Q-ball imaging method was adopted to acquire the diffusion displacements. Human motor pathways with seed points from the internal capsule, motor cortex, and pons were studied respectively. The results were consistent with known anatomy and demonstrated the promising potential of the MFACT method in mapping the complex neuronal architecture in the human brain.