Respiration-induced B0 field fluctuation compensation in balanced SSFP: real-time approach for transition-band SSFP fMRI.
In functional MRI (fMRI) the resonance frequency shift induced from respiration is a major source of physiological noise. In transition-band SSFP fMRI the respiration-induced resonance offset not only increases noise interference, it also shifts the activation band. This leads to a reduction in the contrast-to-noise ratio (CNR) and the potential for varying contrast levels during the experiment. A novel real-time method that compensates for the respiration-induced resonance offset frequency is presented. This method utilizes free induction decay (FID) phase information to measure the resonance offset. For compensation, one can update the resonant frequency in real time by changing the transmit RF pulse and receiver phases to track the measured offset. The results show decreased signal power in the respiration frequency band and increased numbers of activated voxels with higher Z-scores compared to uncompensated experiments.

title: T2*-based fiber orientation mapping
abstract: Recent MRI studies at high field have observed that, in certain white matter fiber bundles, the signal in T(2)*-weighted MRI (i.e. MRI sensitized to apparent transverse relaxivity) is dependent on fiber orientation θ relative to B(0). In this study, the characteristics of this dependency are quantitatively investigated at 7 T using ex-vivo brain specimens, which allowed a large range of rotation angles to be measured. The data confirm the previously suggested variation of R(2)* (=1/T(2)*) with θ and also indicate that this dependency takes the shape of a combination of sin2θ and sin4θ functions, with modulation amplitudes (=ΔR(2)*) reaching 6.44±0.15 Hz (or ΔT(2)*=2.91±0.33 ms) in the major fiber bundles of the corpus callosum. This particular dependency can be explained by a model of local, sub-voxel scale magnetic field changes resulting from magnetic susceptibility sources that are anisotropic. As an illustration of a potential use of the orientation dependence of R(2)*, the feasibility of generating fiber orientation maps from R(2)* data is investigated.

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: The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain
abstract: 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: 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: The critical-size supraalveolar peri-implant defect model: reproducibility in histometric data acquisition of alveolar bone formation and osseointegration.
abstract: The objective of this report is to present the reproducibility of outcomes assessments in the Critical-Size Supraalveolar Peri-Implant Defect Model.



Two examiners without specific experience in histological analysis and one experienced examiner performed the histometric evaluation. A comprehensive training program in data acquisition and histological analysis was established, the inexperienced examiners underwent approximately 12 h of training over multiple sessions. A custom-designed image analysis software macro and a computer-based image system were used to analyse digital images generated by a microscope camera system. Nine parameters for newly formed and resident bone were evaluated. Examiners performed histometric analysis using 36 histologic sections selected from critical-size supraalveolar peri-implant defects in 12 male Hound Labrador Mongrel dogs. Buccal and lingual measurements were performed in 72 sites. Intra- and inter-examiner reproducibility were evaluated using the concordance correlation coefficient (CCC) and means +/- SD of the differences. Systematic errors were evaluated using an F-test for equality of means and variances.



Intra-examiner reproducibility was high for all parameters evaluated, the lowest CCC observed being 0.87. Inter-examiner reproducibility was also high, most CCCs exceeding 0.90. Minor systematic errors for intra- and inter-examiner comparisons were occasionally observed. The results imply a high temporal stability because recordings were performed 3 months apart. Measurement errors were stable throughout the range of observations for all parameters.



High examiner reproducibility and temporal stability can be achieved for histometric data acquisition using the Critical-Size Supraalveolar Peri-Implant Defect Model. Examiner reproducibility should be routinely assessed, reported, and accounted for to assure the quality of evidence generated by preclinical studies.

title: Microthermogravimetry using a microcantilever hot plate with integrated temperature-compensated piezoresistive strain sensors.
abstract: This paper reports thermogravimetric analysis of nanogram samples of paraffin using a microcantilever hot plate. The microcantilever hot plate has an integrated temperature-controlled heater and integrated temperature-compensated strain-sensing piezoresistors. The microcantilever vibration amplitude was measured using either a laser and a position sensitive photodiode, or using the piezoresistors. The cantilever resonance was measured as the cantilever was heated, such that the analyte mass could be measured as a function of temperature. Both optical and piezoresistive methods were employed to generate thermogravimetric curves for analytes in the range of 1-3 ng, and the results of the two methods compared well.

title: Motion correction for phase-resolved dynamic optical coherence tomography imaging of rodent cerebral cortex
abstract: Cardiac and respiratory motions in animals are the primary source of image quality degradation in dynamic imaging studies, especially when using phase-resolved imaging modalities such as spectral-domain optical coherence tomography (SD-OCT), whose phase signal is very sensitive to movements of the sample. This study demonstrates a method with which to compensate for motion artifacts in dynamic SD-OCT imaging of the rodent cerebral cortex. We observed that respiratory and cardiac motions mainly caused, respectively, bulk image shifts (BISs) and global phase fluctuations (GPFs). A cross-correlation maximization-based shift correction algorithm was effective in suppressing BISs, while GPFs were significantly reduced by removing axial and lateral global phase variations. In addition, a non-origin-centered GPF correction algorithm was examined. Several combinations of these algorithms were tested to find an optimized approach that improved image stability from 0.5 to 0.8 in terms of the cross-correlation over 4 s of dynamic imaging, and reduced phase noise by two orders of magnitude in ~8% voxels.

title: Alignment of genetic and physical maps of Gibberella zeae.
abstract: We previously published a genetic map of Gibberella zeae (Fusarium graminearum sensu lato) based on a cross between Kansas strain Z-3639 (lineage 7) and Japanese strain R-5470 (lineage 6). In this study, that genetic map was aligned with the third assembly of the genomic sequence of G. zeae strain PH-1 (lineage 7) using seven structural genes and 108 sequenced amplified fragment length polymorphism markers. Several linkage groups were combined based on the alignments, the nine original linkage groups were reduced to six groups, and the total size of the genetic map was reduced from 1,286 to 1,140 centimorgans. Nine supercontigs, comprising 99.2% of the genomic sequence assembly, were anchored to the genetic map. Eight markers (four markers from each parent) were not found in the genome assembly, and four of these markers were closely linked, suggesting that >150 kb of DNA sequence is missing from the PH-1 genome assembly. The alignments of the linkage groups and supercontigs yielded four independent sets, which is consistent with the four chromosomes reported for this fungus. Two proposed heterozygous inversions were confirmed by the alignments; otherwise, the colinearity of the genetic and physical maps was high. Two of four regions with segregation distortion were explained by the two selectable markers employed in making the cross. The average recombination rates for each chromosome were similar to those previously reported for G. zeae. Despite an inferred history of genetic isolation of lineage 6 and lineage 7, the chromosomes of these lineages remain homologous and are capable of recombination along their entire lengths, even within the inversions. This genetic map can now be used in conjunction with the physical sequence to study phenotypes (e.g., fertility and fitness) and genetic features (e.g., centromeres and recombination frequency) that do not have a known molecular signature in the genome.