Mapping genetic influences on brain fiber architecture with high angular resolution diffusion imaging (HARDI)

We report the first 3D maps of genetic effects on brain fiber complexity. We analyzed HARDI brain imaging data from 90 young adult twins using an information-theoretic measure, the Jensen-Shannon divergence (JSD), to gauge the regional complexity of the white matter fiber orientation distribution functions (ODF). HARDI data were fluidly registered using Karcher means and ODF square-roots for interpol ation; each subject's JSD map was computed from the spatial coherence of the ODFs in each voxel's neighborhood. We evaluated the genetic influences on generalized fiber anisotropy (GFA) and complexity (JSD) using structural equation models (SEM). At each voxel, genetic and environmental components of data variation were estimated, and their goodness of fit tested by permutation. Color-coded maps revealed that the optimal models varied for different brain regions. Fiber complexity was predominantly under genetic control, and was higher in more highly anisotropic regions. These methods show promise for discovering factors affecting fiber connectivity in the brain.

Genetics of brain fiber architecture and intellectual performance

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a 2 = 0.55, p = 0.04, left; a 2 = 0.74, p = 0.006, right), bilateral parietal (a 2 = 0.85, p < 0.001, left; a 2 = 0.84, p < 0.001, right), and left occipital (a 2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto- occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

Information-theoretic analysis of brain white matter fiber orientation distribution functions

We propose a new information-theoretic metric, the symmetric Kullback-Leibler divergence (sKL-divergence), to measure the difference between two water diffusivity profiles in high angular resolution diffusion imaging (HARDI). Water diffusivity profiles are modeled as probability density functions on the unit sphere, and the sKL-divergence is computed from a spherical harmonic series, which greatly reduces computational complexity. Adjustment of the orientation of diffusivity functions is essential when the image is being warped, so we propose a fast algorithm to determine the principal direction of diffusivity functions using principal component analysis (PCA). We compare sKL-divergence with other inner-product based cost functions using synthetic samples and real HARDI data, and show that the sKL-divergence is highly sensitive in detecting small differences between two diffusivity profiles and therefore shows promise for applications in the nonlinear registration and multisubject statistical analysis of HARDI data.

Heritability of white matter fiber tract shapes: A HARDI study of 198 twins

Genetic analysis of diffusion tensor images (DTI) shows great promise in revealing specific genetic variants that affect brain integrity and connectivity. Most genetic studies of DTI analyze voxel-based diffusivity indices in the image space (such as 3D maps of fractional anisotropy) and overlook tract geometry. Here we propose an automated workflow to cluster fibers using a white matter probabilistic atlas and perform genetic analysis on the shape characteristics of fiber tracts. We apply our approach to large study of 4-Tesla high angular resolution diffusion imaging (HARDI) data from 198 healthy, young adult twins (age: 20-30). Illustrative results show heritability for the shapes of several major tracts, as color-coded maps.

The multivariate A/C/E model and the genetics of fiber architecture

We present a new algorithm to compute the voxel-wise genetic contribution to brain fiber microstructure using diffusion tensor imaging (DTI) in a dataset of 25 monozygotic (MZ) twins and 25 dizygotic (DZ) twin pairs (100 subjects total). First, the structural and DT scans were linearly co-registered. Structural MR scans were nonlinearly mapped via a 3D fluid transformation to a geometrically centered mean template, and the deformation fields were applied to the DTI volumes. After tensor re-orientation to realign them to the anatomy, we computed several scalar and multivariate DT-derived measures including the geodesic anisotropy (GA), the tensor eigenvalues and the full diffusion tensors. A covariance-weighted distance was measured between twins in the Log-Euclidean framework [2], and used as input to a maximum-likelihood based algorithm to compute the contributions from genetics (A), common environmental factors (C) and unique environmental ones (E) to fiber architecture. Quanititative genetic studies can take advantage of the full information in the diffusion tensor, using covariance weighted distances and statistics on the tensor manifold.

White matter integrity measured by fractional anisotropy correlates poorly with actual individual fiber anisotropy

Fractional anisotropy (FA), a very widely used measure of fiber integrity based on diffusion tensor imaging (DTI), is a problematic concept as it is influenced by several quantities including the number of dominant fiber directions within each voxel, each fiber's anisotropy, and partial volume effects from neighboring gray matter. High-angular resolution diffusion imaging (HARDI) can resolve more complex diffusion geometries than standard DTI, including fibers crossing or mixing. The tensor distribution function (TDF) can be used to reconstruct multiple underlying fibers per voxel, representing the diffusion profile as a probabilistic mixture of tensors. Here we found that DTIderived mean diffusivity (MD) correlates well with actual individual fiber MD, but DTI-derived FA correlates poorly with actual individual fiber anisotropy, and may be suboptimal when used to detect disease processes that affect myelination. Analysis of the TDFs revealed that almost 40% of voxels in the white matter had more than one dominant fiber present. To more accurately assess fiber integrity in these cases, we here propose the differential diffusivity (DD), which measures the average anisotropy based on all dominant directions in each voxel.

Brain network efficiency and topology depend on the fiber tracking method: 11 tractography algorithms compared in 536 subjects

As connectivity analyses become more popular, claims are often made about how the brain's anatomical networks depend on age, sex, or disease. It is unclear how results depend on tractography methods used to compute fiber networks. We applied 11 tractography methods to high angular resolution diffusion images of the brain (4-Tesla 105-gradient HARDI) from 536 healthy young adults. We parcellated 70 cortical regions, yielding 70×70 connectivity matrices, encoding fiber density. We computed popular graph theory metrics, including network efficiency, and characteristic path lengths. Both metrics were robust to the number of spherical harmonics used to model diffusion (4th-8th order). Age effects were detected only for networks computed with the probabilistic Hough transform method, which excludes smaller fibers. Sex and total brain volume affected networks measured with deterministic, tensor-based fiber tracking but not with the Hough method. Each tractography method includes different fibers, which affects inferences made about the reconstructed networks.

Analyzing multi-fiber reconstruction in high angular resolution diffusion imaging using the tensor distribution function

High-angular resolution diffusion imaging (HARDI) can reconstruct fiber pathways in the brain with extraordinary detail, identifying anatomical features and connections not seen with conventional MRI. HARDI overcomes several limitations of standard diffusion tensor imaging, which fails to model diffusion correctly in regions where fibers cross or mix. As HARDI can accurately resolve sharp signal peaks in angular space where fibers cross, we studied how many gradients are required in practice to compute accurate orientation density functions, to better understand the tradeoff between longer scanning times and more angular precision. We computed orientation density functions analytically from tensor distribution functions (TDFs) which model the HARDI signal at each point as a unit-mass probability density on the 6D manifold of symmetric positive definite tensors. In simulated two-fiber systems with varying Rician noise, we assessed how many diffusionsensitized gradients were sufficient to (1) accurately resolve the diffusion profile, and (2) measure the exponential isotropy (EI), a TDF-derived measure of fiber integrity that exploits the full multidirectional HARDI signal. At lower SNR, the reconstruction accuracy, measured using the Kullback-Leibler divergence, rapidly increased with additional gradients, and EI estimation accuracy plateaued at around 70 gradients.

Fiber Bragg grating accelerometer based on a transversely rotating stick

Fiber Bragg Grating (FBG) accelerometers using transverse forces with an inertial object placed at the middle of the FBG have a high sensitivity but low resonant frequency. The resonant frequency 26 Hz and sensitivity at 6 Hz 1.29 nm/g were reported based on a 50mm-long FBG accelerometer. We demonstrate that the first FBG accelerometer based on a transversely rotating stick, which can, at the same or even larger size, keep the high sensitivity and significantly increase the low resonant frequency. In our experiments, a 77.5mm-long FBG accelerometer has achieved a similar sensitivity but 65% higher resonant frequency. This novel structure not only significantly widens the potential applications of FBG accelerometers by increasing their resonant frequencies but also provides a new route to design other accelerometers, e.g. micro accelerometers.

Nanofiber orientation and surface functionalization modulate human mesenchymal stem cell behavior in vitro

Electrospun nanofiber meshes have emerged as a new generation of scaffold membranes possessing a number of features suitable for tissue regeneration. One of these features is the flexibility to modify their structure and composition to orchestrate specific cellular responses. In this study, we investigated the effects of nanofiber orientation and surface functionalization on human mesenchymal stem cell (hMSC) migration and osteogenic differentiation. We used an in vitro model to examine hMSC migration into a cell-free zone on nanofiber meshes and mitomycin C treatment to assess the contribution of proliferation to the observed migration. Poly (ɛ-caprolactone) meshes with oriented topography were created by electrospinning aligned nanofibers on a rotating mandrel, while randomly oriented controls were collected on a stationary collector. Both aligned and random meshes were coated with a triple-helical, type I collagen-mimetic peptide, containing the glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) motif. Our results indicate that nanofiber GFOGER peptide functionalization and orientation modulate cellular behavior, individually, and in combination. GFOGER significantly enhanced the migration, proliferation, and osteogenic differentiation of hMSCs on nanofiber meshes. Aligned nanofiber meshes displayed increased cell migration along the direction of fiber orientation compared to random meshes; however, fiber alignment did not influence osteogenic differentiation. Compared to each other, GFOGER coating resulted in a higher proliferation-driven cell migration, whereas fiber orientation appeared to generate a larger direct migratory effect. This study demonstrates that peptide surface modification and topographical cues associated with fiber alignment can be used to direct cellular behavior on nanofiber mesh scaffolds, which may be exploited for tissue regeneration.

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Inhibition by poly(acrylic acid) and morphological changes in calcium carbonate and calcium carbonate/calcium sulfate crystallization on silica fibers

An intrinsic exposed core optical fiber sensor (IECOFS) made from fused silica was used to monitor the crystallization of calcium carbonate (CaCO3) and CaCO3/calcium sulfate (CaSO4) composite at 100 and 120 °C in the absence and presence of low-molar-mass (Mn ≤ 2000) poly(acrylic acid) (PAA) with different end groups. The IECOFS responded only to deposition and growth processes on the fiber surface rather than changes occurring in the bulk of the solution. Hexyl isobutyrate-terminated PAA (Mn = 1400) and hexadecyl isobutyrate-terminated PAA (Mn = 1700) were the most effective species in preventing CaCO3 deposition. Phase transformation from vaterite to aragonite/calcite decreased with increasing hydrophobicity of the PAA end group. Low-molar-mass PAA at 10 ppm showed very significant inhibition of CaCO3/CaSO4 composite formation for all end groups investigated.

Energy-based guidance of an underactuated unmanned underwater vehicle on a helical trajectory

This paper presents a motion control system for guidance of an underactuated Unmanned Underwater Vehicle (UUV) on a helical trajectory. The control strategy is developed using Port-Hamiltonian theory and interconnection and damping assignment passivity-based control. Using energy routing, the trajectory of a virtual fully actuated plant is guided onto a vector field. A tracking controller is then used that commands the underactuated plant to follow the velocity of the virtual plant. An integral control is inserted between the two control layers, which adds robustness and disturbance rejection to the design.

Esophageal stricture in children: Fiber-optic endoscopy and dilatation under fluoroscopic control

We made a retrospective analysis of the efficacy and complication rate of 268 esophageal dilatation procedures performed under fluoroscopic control using the fiber-optic endoscope in 45 children with esophageal stricture. Antegrade and retrograde stricture dilatation was performed under general anesthetic, mainly as an outpatient procedure. Thirty-six children had an esophageal stricture following tracheoesophageal fistula and/or esophageal atresia repair, and nine children had severe corrosive stricture of the esophagus following lye ingestion. The procedure was well tolerated and effective. © 1992 Raven Press, Ltd., New York.

A multiscale study on the structural and mechanical properties of the luffa sponge from Luffa cylindrica plant

Cellular materials that are often observed in biological systems exhibit excellent mechanical properties at remarkably low densities. Luffa sponge is one of such materials with a complex interconnecting porous structure. In this paper, we studied the relationship between its structural and mechanical properties at different levels of its hierarchical organization from a single fiber to a segment of whole sponge. The tensile mechanical behaviors of three single fibers were examined by an Instron testing machine and the ultrastructure of a fractured single fiber was observed in a scanning electronic microscope. Moreover, the compressive mechanical behaviors of the foam-like blocks from different locations of the sponge were examined. The difference of the compressive stress-strain responses of four sets of segmental samples were also compared. The result shows that the single fiber is a porous composite material mainly consisting of cellulose fibrils and lignin/hemicellulose matrix, and its Young's modulus and strength are comparable to wood. The mechanical behavior of the block samples from the hoop wall is superior to that from the core part. Furthermore, it shows that the influence of the inner surface on the mechanical property of the segmental sample is stronger than that of the core part; in particular, the former's Young's modulus, strength and strain energy absorbed are about 1.6 times higher. The present work can improve our understanding of the structure-function relationship of the natural material, which may inspire fabrication of new biomimetic foams with desirable mechanical efficiency for further applications in anti-crushing devices and super-light sandwich panels.