White matter of the brain has been demonstrated to have multiple relaxation components. Among them, the short transverse relaxation time component (T2 < 40 ms; T2* < 25 ms at 3T) has been suggested to originate from myelin water whereas long transverse relaxation time components have been associated with axonal and/or interstitial water. In myelin water imaging, T2 or T2* signal decay is measured to estimate myelin water fraction based on T2 or T2* differences among the water components. This method has been demonstrated to be sensitive to demyelination in the brain but suffers from low SNR and image artifacts originating from ill-conditioned multi-exponential fitting. In this study, a novel approach that selectively acquires short transverse relaxation time signal is proposed. The method utilizes a double inversion RF pair to suppress a range of long T1 signal. This suppression leaves short T2* signal, which has been suggested to have short T1, as the primary source of the image. The experimental results confirms that after suppression of long T1 signals, the image is dominated by short T2* in the range of myelin water, allowing us to directly visualize the short transverse relaxation time component in the brain. Compared to conventional myelin water imaging, this new method of direct visualization of short relaxation time component (ViSTa) provides high quality images. When applied to multiple sclerosis patients, chronic lesions show significantly reduced signal intensity in ViSTa images suggesting sensitivity to demyelination.
background suppression; multiple water components in white matter; myelin water imaging; T1 of myelin water; T1 filter
Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH.
Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding.
Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 ± 0.8 vs. 33.2 ± 2.0 vs. 26.6 ± 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 ± 0.20% vs. 5.26 ± 3.12% vs. 4.03 ± 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028).
In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.
Left ventricular hypertrophy; Aortic banding; Debanding
The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.
Polynucleotides; Polydeoxyribonucleotides; Rejuvenation; Wound Healing
The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN) that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs). There are two excitatory inputs to DN, mossy fiber and climbing fiber collaterals, but neither of them appears to have sufficient strength for generation of burst activity in DN. Therefore, we can assume two possible mechanisms: post-inhibitory rebound excitation and disinhibition. If rebound excitation works, phasic excitation of PCs and a concomitant inhibition of DN cells should precede the excitation of DN cells. On the other hand, if disinhibition plays a primary role, phasic suppression of PCs and activation of DN cells should be observed at the same timing. To examine these two hypotheses, we compared the activity patterns of PCs in the cerebrocerebellum and DN cells during step-tracking wrist movements in three Japanese monkeys. As a result, we found that the majority of wrist-movement-related PCs were suppressed prior to movement onset and the majority of wrist-movement-related DN cells showed concurrent burst activity without prior suppression. In a minority of PCs and DN cells, movement-related increases and decreases in activity, respectively, developed later. These activity patterns suggest that the initial burst activity in DN cells is generated by reduced inhibition from PCs, i.e., by disinhibition. Our results indicate that suppression of PCs, which has been considered secondary to facilitation, plays the primary role in generating outputs from DN. Our findings provide a new perspective on the mechanisms used by PCs to influence limb motor control and on the plastic changes that underlie motor learning in the cerebrocerebellum.
Recent MRI studies have demonstrated that the relative orientation of white matter fibers to the B0 field significantly affects
R2∗ measurement. In this work, the origin of this effect was investigated by measuring R2 and
R2∗ in multiple orientations and fitting the results to magnetic susceptibility-based models and magic angle-based models. To further explore the source of magnetic susceptibility effect, the contribution of tissue iron to the orientation dependent
R2∗ contrast was investigated. Additionally, the effects of temperature on
R2∗ and orientation dependent
R2∗ contrasts were studied to understand the differences reported between a fixed specimen at room temperature and in vivo at body temperature. The results suggest that the B0 dependent
R2∗ variation is better explained by the magnetic susceptibility-based model with susceptibility anisotropy. However, extracting tissue iron did not reduce the orientation dependent
R2∗ contrast, suggesting iron is not the origin of the contrast. This leaves susceptibility effects from myelin as the most probable origin of the contrast. Temperature showed large contribution on both
R2∗ and orientation dependent
R2∗ contrasts, explaining a portion of the contrast difference between the in-vivo and in-vitro conditions.
Magnetic susceptibility anisotropy; Magic angle effects; B0 orientation dependent transverse magnetization (T2 and
T2∗); MRI relaxometry
Effective point-of-use devices for providing safe drinking water are urgently needed to reduce the global burden of waterborne disease. Here we show that plant xylem from the sapwood of coniferous trees – a readily available, inexpensive, biodegradable, and disposable material – can remove bacteria from water by simple pressure-driven filtration. Approximately 3 cm3 of sapwood can filter water at the rate of several liters per day, sufficient to meet the clean drinking water needs of one person. The results demonstrate the potential of plant xylem to address the need for pathogen-free drinking water in developing countries and resource-limited settings.
Direct measurement of neural currents by means of MRI (ncMRI) can potentially open a high temporal resolution (10-100 ms) window applicable for monitoring dynamics of neurnal activity without loss of the high spatial resolution afforded by MRI. Previously we have shown that the alternating balanced steady states (ABSS) imaging affords high sensitivity to weak periodic currents owing to its amplification of periodic spin phase perturbations. This technique, however, requires precise synchronization of such perturbations to the RF pulses. Herein we extend ABSS imaging to multiple balanced alternating steady states (MASS) for estimation of neural current waveforms. Simulations and phantom experiments show that the off-resonance profile of the MASS signal carries information about the frequency content of driving waveforms. In addition, the method is less sensitive than ABSS to precise waveform timing relative to RF pulses. Thus MASS is potentially applicable to MR imaging of the waveforms of periodic neuronal activity.
balanced SSFP; multiple alternating steady states; neural current MRI; MR-encephalography
T2*-weighted gradient-echo MRI images at high field (≥ 7 Tesla) 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 T2* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T2* 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 T2* 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 T2* and frequency contrasts.
T2* decay; R2* relaxation; phase image; resonance frequency image; demyelination; cuprizone; formalin fixation
Visualizing myelin in human brain may help the study of diseases such as multiple sclerosis. Previous studies based on T1 and T2 relaxation contrast have suggested the presence of a distinct water pool that may report directly on local myelin content. Recent work indicates that T2* contrast may offer particular advantages over T1 and T2 contrast, especially at high field. However, the complex mechanism underlying T2* relaxation may render interpretation difficult.
To address this issue, T2* relaxation behavior in human brain was studied at 3 and 7 tesla. Multiple gradient echoes covering most of the decay curve were analyzed for deviations from mono-exponential behavior. The data confirm the previous finding of a distinct rapidly relaxing signal component (T2* ~ 6 ms), tentatively attributed to myelin water. However, in extension to previous findings, this rapidly relaxing component displayed a substantial resonance frequency shift, reaching 36 Hz in the corpus callosum at 7 T. The component’s fractional amplitude and frequency shift appeared to depend on both field strength and fiber orientation, consistent with a mechanism originating from magnetic susceptibility effects. The findings suggest that T2* contrast at high field may be uniquely sensitive to tissue myelin content, and that proper interpretation will require modeling of susceptibility-induced resonance frequency shifts.
T2* relaxation; high field imaging; myelin water fraction; white matter imaging
There is a long history and a growing interest in the canine as a subject of study in neuroscience research and in translational neurology. In the last few years, anatomical and functional magnetic resonance imaging (MRI) studies of awake and anesthetized dogs have been reported. Such efforts can be enhanced by a population atlas of canine brain anatomy to implement group analyses. Here we present a canine brain atlas derived as the diffeomorphic average of a population of fifteen mesaticephalic dogs. The atlas includes: 1) A brain template derived from in-vivo, T1-weighted imaging at 1 mm isotropic resolution at 3 Tesla (with and without the soft tissues of the head); 2) A co-registered, high-resolution (0.33 mm isotropic) template created from imaging of ex-vivo brains at 7 Tesla; 3) A surface representation of the gray matter/white matter boundary of the high-resolution atlas (including labeling of gyral and sulcal features). The properties of the atlas are considered in relation to historical nomenclature and the evolutionary taxonomy of the Canini tribe. The atlas is available for download (https://cfn.upenn.edu/aguirre/wiki/public:data_plosone_2012_datta).
In MRI of the human brain, subject motion is a major cause of magnetic resonance image quality degradation. To compensate for the effects of head motion during data acquisition, an in-bore optical motion tracking system is proposed. The system comprises two MR compatible infrared cameras that are fixed on a holder right above and in front of the head coil. The resulting close proximity of the cameras to the object allows precise tracking of its movement. During image acquisition, the MRI scanner uses this tracking information to prospectively compensate for head motion by adjusting gradient field direction and RF phase and frequency. Experiments performed on subjects demonstrate robust system performance with translation and rotation accuracies of 0.1 mm and 0.15° respectively.
prospective motion correction; optical tracking; MR compatible camera; real-time MRI
The generally accepted treatment for infected aortic aneurysms involves open surgical resection and debridement, with in situ or extra-anatomical bypass. Occasionally, endovascular management can be substituted for the standard operation dependent on the patient's condition. We report the case of an 81-year-old female with a ruptured infected aortic aneurysm and sepsis, successfully treated endovascularly. She had been on oral antibiotics for one year and is doing well 2 years after discharge.
Ruptured aneurysm; Sepsis; Endovascular treatment
Recent MRI studies at high field have observed that, in certain white matter fiber bundles, the signal in T2*-weighted MRI (i.e. MRI sensitized to apparent transverse relaxivity) is dependent on fiber orientation θ relative to B0. 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 R2* (= 1/T2*) with θ and also indicate that this dependency takes the shape of a combination of sin2θ and sin4θ functions, with modulation amplitudes (= ΔR2*) reaching 6.44 ± 0.15 Hz (or ΔT2* = 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 R2*, the feasibility of generating fiber orientation maps from R2* data is investigated.
T2* relaxation; R2*; fiber tracking; magnetic susceptibility anisotropy in white matter; susceptibility tensor imaging (STI); diffusion tensor imaging (DTI)
Recent MRI studies have exploited subtle magnetic susceptibility differences between brain tissues to improve anatomical contrast and resolution. These susceptibility differences lead to resonance frequency shifts which can be visualized by reconstructing the signal phase in conventional gradient echo (GRE) acquisition techniques. In this work, a method is proposed to improve the contrast to noise ratio per unit time (CNR efficiency) of anatomical MRI based on resonance frequency contrast. The method, based on the balanced steady state free precession (bSSFP) MRI acquisition technique, was evaluated in its ability to generate contrast between gray and white matter in human brain at 3T and 7T. The results show substantially improved CNR efficiency of bSSFP phase images (2.85 ± 0.21 times at 3 T and 1.71 ± 0.11 times at 7 T) compared to the GRE data in a limited spatial area. This limited spatial coverage is attributed to the sensitivity of bSSFP to macroscopic B0 inhomogeneities. With this CNR improvement, high resolution bSSFP phase images (resolution = 0.3 × 0.3 × 2 mm3, acquisition time = 10 min) acquired at 3 T had sufficient CNR to allow the visualization of cortical laminar structures in in-vivo human primary visual cortex. Practical application of the proposed method may require improvement of B0 homogeneity and stability by additional preparatory scans and/or compensation schemes such as respiration and drift compensation. Without these additions, the CNR benefits of the method may be limited to studies at low field or limited regions of interest.
ultra high field MRI; MR microscopy; balanced SSFP and GRE sequence comparison; 7 Tesla
Procedural motor learning includes a period when no substantial gain in performance improvement is obtained even with repeated, daily practice. Prompted by the potential benefit of high-frequency transcutaneous electrical stimulation, we examined if the stimulation to the hand reduces redundant motor activity that likely exists in an acquired hand motor skill, so as to further upgrade stable motor performance. Healthy participants were trained until their motor performance of continuously rotating two balls in the palm of their right hand became stable. In the series of experiments, they repeated a trial performing this cyclic rotation as many times as possible in 15 s. In trials where we applied the stimulation to the relaxed thumb before they initiated the task, most reported that their movements became smoother and they could perform the movements at a higher cycle compared to the control trials. This was not possible when the dorsal side of the wrist was stimulated. The performance improvement was associated with reduction of amplitude of finger displacement, which was consistently observed irrespective of the task demands. Importantly, this kinematic change occurred without being noticed by the participants, and their intentional changes of motor strategies (reducing amplitude of finger displacement) never improved the performance. Moreover, the performance never spontaneously improved during one-week training without stimulation, whereas the improvement in association with stimulation was consistently observed across days during training on another week combined with the stimulation. The improved effect obtained in stimulation trials on one day partially carried over to the next day, thereby promoting daily improvement of plateaued performance, which could not be unlocked by the first-week intensive training. This study demonstrated the possibility of effectively improving a plateaued motor skill, and pre-movement somatic stimulation driving this behavioral change.
High field (≥ 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.
phase contrast image; deoxy-hemoglobin; high field; USPIO; iron oxide nano-particle
In this article, 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 3 T with contrast 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 eliminate or reduce the size of banding artifacts. The method can be used to increase the SNR in bSSFP imaging or to increase the functional contrast in bSSFP fMRI by allowing a longer usable repetition time (TR).
min-max; minimax; least-squares; shimming; shim; SSFP
Stem cell transplantation is expected to have good effects in the treatment of myocardial infarction (MI). We tested the effect of the transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats with myocardial infarctions.
Materials and Methods
ASCs were isolated from the waste of elective abdominal surgery. The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. One week after MI, either 1 × 106 ASCs or an equal volume of phosphate-buffered saline (PBS) was injected into the infarct zone. Cardiac function was assessed by echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks after transplantation, immunohistochemistry was performed.
Left ventricular function, including fractional shortening (FS), and ejection fraction (EF) showed a significant improvement in the ASCs transplantation group compared to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness of the left ventricle was significantly thicker in the ASCs transplantation group compared to the PBS group (p < 0.01). Multiple troponin T staining, and irregular, small amounts of connexin 43 expression also was observed in the ASCs transplantation group. Infarcted myocardium showed higher capillary density in the ASCs transplantation group than in the PBS injected group (p < 0.01).
This study provides encouraging evidence that transplantation of ASCs can improve cardiac function of infarct myocardium in rat models with a limitation of cardiac remodeling, improved wall thickness, and increased neovascularization.
Myocardial infarction; stem cells; transplantation
The adhesive pads of geckos provide control of normal adhesive force by controlling the applied shear force. This frictional adhesion effect is one of the key principles used for rapid detachment in animals running up vertical surfaces. We developed polypropylene microfibre arrays composed of vertical, 0.3 μm radius fibres with elastic modulus of 1 GPa which show this effect for the first time using a stiff polymer. In the absence of shear forces, these fibres show minimal normal adhesion. However, sliding parallel to the substrate with a spherical probe produces a frictional adhesion effect which is not seen in the flat control. A cantilever model for the fibres and the spherical probe indicates a strong dependence on the initial fibre angle. A novel feature of the microfibre arrays is that adhesion improves with use. Repeated shearing of fibres temporarily increases maximum shear and pull-off forces.
bio-inspired adhesion; gecko; frictional adhesion; shear
Gecko-inspired microfibre arrays with 42 million polypropylene fibres cm−2 (each fibre with elastic modulus 1 GPa, length 20 μm and diameter 0.6 μm) were fabricated and tested under pure shear loading conditions, after removing a preload of less than 0.1 N cm−2. After sliding to engage fibres, 2 cm2 patches developed up to 4 N of shear force with an estimated contact region of 0.44 cm2. The control unfibrillated surface had no measurable shear force. For comparison, a natural setal patch tested under the same conditions on smooth glass showed approximately seven times greater shear per unit estimated contact region. Similar to gecko fibre arrays, the synthetic patch maintains contact and increases shear force with sliding. The high shear force observed (approx. 210 nN per fibre) suggests that fibres are in side contact, providing a larger true contact area than would be obtained by tip contact. Shear force increased over the course of repeated tests for synthetic patches, suggesting deformation of fibres into more favourable conformations.
bio-inspired adhesion; gecko; friction; shear; sliding