The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain
T(2)*-weighted gradient-echo MRI images at high field (≥ 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts.

title: Sensitivity of MRI resonance frequency to the orientation of brain tissue microstructure
abstract: Recent advances in high-field (≥7 T) MRI have made it possible to study the fine structure of the human brain at the level of fiber bundles and cortical layers. In particular, techniques aimed at detecting MRI resonance frequency shifts originating from local variation in magnetic susceptibility and other sources have greatly improved the visualization of these structures. A recent theoretical study [He X, Yablonskiy DA (2009) Proc Natl Acad Sci USA 106:13558–13563] suggests that MRI resonance frequency may report not only on tissue composition, but also on microscopic compartmentalization of susceptibility inclusions and their orientation relative to the magnetic field. The proposed sensitivity to tissue structure may greatly expand the information available with conventional MRI techniques. To investigate this possibility, we studied postmortem tissue samples from human corpus callosum with an experimental design that allowed separation of microstructural effects from confounding macrostructural effects. The results show that MRI resonance frequency does depend on microstructural orientation. Furthermore, the spatial distribution of the resonance frequency shift suggests an origin related to anisotropic susceptibility effects rather than microscopic compartmentalization. This anisotropy, which has been shown to depend on molecular ordering, may provide valuable information about tissue molecular structure.

title: On the contribution of deoxy-hemoglobin to MRI gray–white matter phase contrast at high field
abstract: High field (> or =7 T) MRI studies based on signal phase have been used to improve visualization of the fine structure of the brain, most notably the major white matter fiber bundles, the gray-white matter subdivision, and the laminar cortical architecture. The observed contrast has been attributed in part to local variations in magnetic susceptibility arising from iron in storage proteins and tissue lipid. Another contribution could come from the paramagnetic blood constituent deoxy-hemoglobin, the tissue concentration of which may vary through local variations in vascular density. To investigate this possibility, we examined phase contrast between gray and white matter in rats after intravenous administration of a superparamagnetic contrast agent at various dosages. At the maximum dosage (3 mg Fe/kg), which resulted in an estimated paramagnetic susceptibility shift 4-8 times larger than deoxy-hemoglobin, we observed a negligible increase in phase contrast between gray and white matter. This result suggests that endogenous deoxy-hemoglobin has no significant contribution to phase contrast between gray and white matter.

title: Complex data analysis in high-resolution SSFP fMRI.
abstract: In transition-band steady-state free precession (SSFP) functional MRI (fMRI), functional contrast originates from a bulk frequency shift induced by a deoxygenated hemoglobin concentration change in the activated brain regions. This frequency shift causes a magnitude and/or phase-signal change depending on the off-resonance distribution of a voxel in the balanced-SSFP (bSSFP) profile. However, in early low-resolution studies, only the magnitude signal activations were shown. In this paper the task-correlated phase-signal change is presented in a high-resolution (1 x 1 x 1 mm3) study. To include this phase activation in a functional analysis, a new complex domain data analysis method is proposed. The results show statistically significant phase-signal changes in a large number of voxels comparable to that of the magnitude-activated voxels. The complex-data analysis method successfully includes these phase activations in the activation map and thus provides wider coverage compared to magnitude-data analysis results.

title: Improved shim method based on the minimization of the maximum off-resonance frequency for balanced steady-state free precession (bSSFP).
abstract: In this work, a shim method that minimizes the maximum off-resonance frequency (min-max shim) in balanced steady-state free precession (bSSFP) is tested for brain imaging at 3T with constant and linear shim terms. The method demonstrates improvement of spatial coverage and banding artifact reduction over standard least-squares shimming. In addition, a new method (modified min-max shim) is introduced. This method reduces boundary band regions where the artifact is inevitable due to the excessive off-resonance frequency distribution. In comparison to standard least-squares shimming, the min-max based shim method either eliminates or reduces the size of banding artifacts. The method can be used to increase the signal-to-noise ratio (SNR) in bSSFP imaging or to increase the functional contrast in bSSFP functional MRI (fMRI) by allowing a longer usable repetition time (TR).

title: In vitro peptide release from liquid crystalline buccal delivery systems.
abstract: Swelling and [D-Ala(2), D-Leu(5)]enkephalin (DADLE) release from the lamellar and cubic liquid crystalline phases of glyceryl monooleate (GMO) were studied using two in vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and glyceryl monooleate (0% w/w water content) and DADLE release from the liquid crystalline phases were temperature dependent. The swelling ratio was greater at 20 degrees C than 37 degrees C while DADLE release increased at 37 degrees C compared to 20 degrees C for both the lamellar and cubic phases. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. However, DADLE release increased with increasing initial water content, which corresponded to increased viscosity. The swelling and DADLE release profiles obtained using a Franz cell method with a moist nylon membrane to mimic buccal drug release conditions were slower than the total immersion method. These results show that the swelling and DADLE release strongly depended on temperature, the initial water content of the liquid crystalline matrix and the methodology employed for determining the swelling and DADLE release.

title: Spectrum measurement of fast optical signal of neural activity in brain tissue and its theoretical origin
abstract: Functional brain imaging technologies have enabled recent advances in understanding human brain function. In particular, a noninvasive and fast optical technique will become one of the most promising tools for future studies. As a fundamental ex vivo study for the development of such a technique, this paper demonstrates the spectral measurement of fast optical changes associated with neural activity in bulk brain tissue. For this purpose, a high-speed confocal near-infrared spectrometer was built and used. The results verified that observed transient optical responses (tORs) are associated with neural activity by showing that the following: tORs were concurrent and correlated with local field potentials (LFPs); tORs disappeared following tetrodotoxin application; and tORs were reproducibly observed across preparations. In addition, the amplitude of tORs was statistically significantly larger in longer wavelengths (approximately 1200 nm). The time course of tORs, however, is quite different from that of LFPs. Since this difference implies that tORs may originate not directly from the electric potential variation but from other neurophysiological events accompanying excitation, this paper tested the hypothesis that tORs are attributed to transient cellular volume changes (tCVCs). With no previous dynamic equation to elucidate such different temporal dynamics of the optical responses, a novel mathematical neuron model to describe tCVCs was developed. This neuron model, along with finite-difference time-domain simulations, showed that tCVCs and tORs were similar in the temporal dynamics, order of magnitude, response direction, and detectability in the bulk tissue; thus supporting the hypothesis.

title: High Levels of Sequence Diversity in the 5′ UTRs of Human-Specific L1 Elements
abstract: Approximately 80 long interspersed element (LINE-1 or L1) copies are able to retrotranspose actively in the human genome, and these are termed retrotransposition-competent L1s. The 5′ untranslated region (UTR) of the human-specific L1 contains an internal promoter and several transcription factor binding sites. To better understand the effect of the L1 5′ UTR on the evolution of human-specific L1s, we examined this population of elements, focusing on the sequence diversity and accumulated substitutions within their 5′ UTRs. Using network analysis, we estimated the age of each L1 component (the 5′ UTR, ORF1, ORF2, and 3′ UTR). Through the comparison of the L1 components based on their estimated ages, we found that the 5′ UTR of human-specific L1s accumulates mutations at a faster rate than the other components. To further investigate the L1 5′ UTR, we examined the substitution frequency per nucleotide position among them. The results showed that the L1 5′ UTRs shared relatively conserved transcription factor binding sites, despite their high sequence diversity. Thus, we suggest that the high level of sequence diversity in the 5′ UTRs could be one of the factors controlling the number of retrotransposition-competent L1s in the human genome during the evolutionary battle between L1s and their host genomes.

title: The effect of storage conditions on the permeability of porcine buccal mucosa
abstract: The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.

title: Microcantilever actuation via periodic internal heating.
abstract: This paper reports electrothermal actuation of silicon microcantilevers having integrated resistive heaters. Periodic electrical excitation induced periodic resistive heating in the cantilever, while the cantilever deflection was monitored with a photodetector. Excitation was either at the cantilever resonant frequency, f(0), f(0)/2, or f(0)/3. When the time averaged maximum cantilever temperature was 174 degrees C, the cantilever out-of-plane actuation amplitude was 484 nm near the cantilever resonance frequency of 24.9 kHz. This actuation was sufficiently large to operate the cantilever in intermittent contact mode and scan a calibration grating of height of 20 nm.