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.

Delay tolerant routing protocols for energy-neutral animal tracking

This paper investigates communication protocols for relaying sensor data from animal tracking applications back to base stations. While Delay Tolerant Networks (DTNs) are well suited to such challenging environments, most existing protocols do not consider the available energy that is particularly important when tracking devices can harvest energy. This limits both the network lifetime and delivery probability in energy-constrained applications to the point when routing performance becomes worse than using no routing at all. Our work shows that substantial improvement in data yields can be achieved through simple yet efficient energy-aware strategies. Conceptually, there is need for balancing the energy spent on sensing, data mulling, and delivery of direct packets to destination. We use empirical traces collected in a flying fox (fruit bat) tracking project and show that simple threshold-based energy-aware strategies yield up to 20% higher delivery rates. Furthermore, these results generalize well for a wide range of operating conditions.

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.

Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging

Bone diseases such as rickets and osteoporosis cause significant reduction in bone quantity and quality, which leads to mechanical abnormalities. However, the precise ultrastructural mechanism by which altered bone quality affects mechanical properties is not clearly understood. Here we demonstrate the functional link between altered bone quality (reduced mineralization) and abnormal fibrillar-level mechanics using a novel, real-time synchrotron X-ray nanomechanical imaging method to study a mouse model with rickets due to reduced extrafibrillar mineralization. A previously unreported N-ethyl-N-nitrosourea (ENU) mouse model for hypophosphatemic rickets (Hpr), as a result of missense Trp314Arg mutation of the phosphate regulating gene with homologies to endopeptidase on the X chromosome (Phex) and with features consistent with X-linked hypophosphatemic rickets (XLHR) in man, was investigated using in situ synchrotron small angle X-ray scattering to measure real-time changes in axial periodicity of the nanoscale mineralized fibrils in bone during tensile loading. These determine nanomechanical parameters including fibril elastic modulus and maximum fibril strain. Mineral content was estimated using backscattered electron imaging. A significant reduction of effective fibril modulus and enhancement of maximum fibril strain was found in Hpr mice. Effective fibril modulus and maximum fibril strain in the elastic region increased consistently with age in Hpr and wild-type mice. However, the mean mineral content was ∼21% lower in Hpr mice and was more heterogeneous in its distribution. Our results are consistent with a nanostructural mechanism in which incompletely mineralized fibrils show greater extensibility and lower stiffness, leading to macroscopic outcomes such as greater bone flexibility. Our study demonstrates the value of in situ X-ray nanomechanical imaging in linking the alterations in bone nanostructure to nanoscale mechanical deterioration in a metabolic bone disease. Copyright

Structures of three different neutral polysaccharides of Acinetobacter baumannii, NIPH190, NIPH201, and NIPH615, assigned to K30, K45, and K48 capsule types, respectively, based on capsule biosynthesis gene clusters

Neutral capsular polysaccharides (CPSs) were isolated from Acinetobacter baumannii NIPH190, NIPH201, and NIPH615. The CPSs were found to contain common monosaccharides only and to be branched with a side-chain 1→3-linked β-d-glucopyranose residue. Structures of the oligosaccharide repeat units (K units) of the CPSs were elucidated by 1D and 2D 1H and 13C NMR spectroscopy. Novel CPS biosynthesis gene clusters, designated KL30, KL45, and KL48, were found at the K locus in the genome sequences of NIPH190, NIPH201, and NIPH615, respectively. The genetic content of each gene cluster correlated with the structure of the CPS unit established, and therefore, the capsular types of the strains studied were designated as K30, K45, and K48, respectively. The initiating sugar of each K unit was predicted, and glycosyltransferases encoded by each gene cluster were assigned to the formation of the linkages between sugars in the corresponding K unit.

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.

Catalytic transformation of aliphatic alcohols to corresponding esters in O2 under neutral conditions using visible-light irradiation

Selective oxidation of aliphatic alcohols under mild and base-free conditions is a challenging process for organic synthesis. Herein, we report a one-pot process for the direct oxidative esterification of aliphatic alcohols that is significantly enhanced by visible-light irradiation at ambient temperatures. The new methodology uses heterogenerous photocatalysts of gold–palladium alloy nanoparticles on a phosphate-modified hydrotalcite support and molecular oxygen as a benign oxidant. The alloy photocatalysts can absorb incident light, and the light-excited metal electrons on the surface of metal nanoparticles can activate the adsorbed reactant molecules. Tuning the light intensity and wavelength of the irradiation can remarkably change the reaction activity. Shorter wavelength light (<550 nm) drives the reaction more efficiently than light of longer wavelength (e.g., 620 nm), especially at low temperatures. The phosphate-exchanged hydrotalcite support provides sufficient basicity (and buffer) for the catalytic reactions; thus, the addition of base is not required. The photocatalysts are efficient and readily recyclable. The findings reveal the first example of using “green” oxidants and light energy to drive direct oxidative esterification of aliphatic alcohols under base-free, mild conditions.

The hazards of automatic-dishwasher detergent

Automatic-dishwasher detergent is a common household substance which is extremely corrosive and potentially fatal if ingested. In this report, we discuss the implications of the ingestion of automatic-dishwasher detergent in 18 children over a three-year period. Ten of the 18 children gained access to the automatic-dishwasher detergent from the dishwasher on the completion of the washing-cycle, while the remainder ingested the detergent directly from the packet. There was a poor correlation between the presenting signs and symptoms and the subsequent endoscopic finding in the 14 children who underwent endoscopy.

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.