A systematic correlation between finite element models (FEMs) and histopathology is needed to define deformation thresholds associated with traumatic brain injury (TBI). In this study, a FEM of a transected piglet brain was used to reverse engineer the range of optimal shear moduli for infant (5-day-old, 553-658 Pa) and 4-week old toddler piglet brain, (692-811 Pa) from comparisons with measured in situ tissue strains. The more mature brain modulus was found to have significant strain and strain rate dependencies not observed with the infant brain.
Age-appropriate FEMs were then used to simulate experimental TBI in infant (n=36) and pre-adolescent (n=17) piglets undergoing a range of rotational head loads. The experimental animals were evaluated for the presence of clinically significant traumatic axonal injury (TAI), which was then correlated with FEM-calculated measures of overall and white matter tract-oriented tissue deformations, and used to identify the metric with the highest sensitivity and specificity for detecting TAI. The best predictors of TAI were the tract-oriented strain (6–7%), strain rate (38–40 s−1), and strain times strain rate (1.3–1.8 s−1) values exceeded by 90% of the brain. These tract-oriented strain and strain rate thresholds for TAI were comparable to those found in isolated axonal stretch studies. Furthermore, we proposed that the higher degree of agreement between tissue distortion aligned with white matter tracts and TAI may be the underlying mechanism responsible for more severe TAI after horizontal and sagittal head rotations in our porcine model of nonimpact TAI than coronal plane rotations.
traumatic brain injury; finite element modeling; porcine; pediatric; sports-related head injury; diffusion tensor imaging
To demonstrate the phase evolutions of direct visualization of short transverse relaxation time component (ViSTa) matches with those of myelin water.
Myelin water imaging (MWI) measures short transverse signals, and has been suggested as a biomarker for myelin. Recently, a new approach, ViSTa, has been proposed to acquire short T2* signals by suppressing long T1 signals. This method does not require any ill-conditioned data processing and therefore, provides high quality images. In this work, the phase of the ViSTa signal is explored and compared with the phase of myelin water simulated by the magnetic susceptibility model of hollow cylinder.
The phase evolutions of the ViSTa signal show great similarity to the simulated myelin water phase evolutions. When fiber orientation is perpendicular relative to the main magnetic field, both the ViSTa and the simulated myelin water phase show large positive frequency shifts, whereas the GRE phase shows a slightly negative frequency shift. Additionally, the myelin water phase map generated using DTI information shows a good match with the ViSTa phase image.
These results support the origin of ViSTa signal as myelin water. ViSTa phase may potentially provide sensitivity to demyelination.
myelin water imaging; ViSTa phase imaging; frequency shift; microstructure in white mater; magnetic susceptibility of myelin; hollow cylinder model
Substantial changes have occurred in the Information Technology (IT) sectors and with these changes, the demand for remote access to field sensor information has increased. This allows visualization, monitoring, and control through various electronic devices, such as laptops, tablets, i-Pads, PCs, and cellular phones. The smart phone is considered as a more reliable, faster and efficient device to access and monitor industrial systems and their corresponding information interfaces anywhere and anytime. This study describes the deployment of a protocol whereby industrial system information can be securely accessed by cellular phones via a Supervisory Control And Data Acquisition (SCADA) server. To achieve the study goals, proprietary protocol interconnectivity with non-proprietary protocols and the usage of interconnectivity services are considered in detail. They support the visualization of the SCADA system information, and the related operations through smart phones. The intelligent sensors are configured and designated to process real information via cellular phones by employing information exchange services between the proprietary protocol and non-proprietary protocols. SCADA cellular access raises the issue of security flaws. For these challenges, a cryptography-based security method is considered and deployed, and it could be considered as a part of a proprietary protocol. Subsequently, transmission flows from the smart phones through a cellular network.
cellular protocols and networks; intelligent sensor networks; supervisory control and data acquisition system; security issues; embedded protocol security; information analysis and visualization; Human Machine Interface; transmission flows
Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1.
cytokine; insulin; interleukin 1 (IL-1); protein motif; toll/interleukin-1 receptor (TIR)*
Bar displacement is one of the most common and serious complications after the Nuss procedure. However, measurements of and factors affecting bar displacement have not been reported. The objectives of this study were to develop a decision model to guide surgeons considering repeat treatment and to estimate optimal cut-off values to determine whether reoperation to correct bar displacement is warranted.
From July 2011 to August 2013, ninety bars were inserted in 61 patients who underwent Nuss procedures for pectus excavatum. Group A did not need surgical intervention and Group B required reoperation for bar displacement. Bar position was measured as the distance from the posterior superior end of the sternal body to the upper border of the metal bar on lateral chest radiographs. The bar displacement index (BDI) was calculated using D0 - Dx / D0 x 100 (D0: bar position the day after surgery; Dx: minimal or maximal distance of bar position on the following postoperative days). The optimal cut-off values of BDI warranting reoperation were assessed on the basis of ROC curve analysis.
Of the 61 patients, 32 had single bars inserted whereas 29 had parallel bars inserted. There was a significant difference in age (14.0 ± 7.5 vs. 23.3 ± 12.0, p = 0.0062), preoperative Haller index (HI) (4.0 ± 1.1 vs. 5.0 ± 1.0, p = 0.033), and postoperative HI (2.7 ± 0.4 vs. 3.2 ± 0.5 p = 0.006) between the two groups. The optimal cut-off value of BDI was 8.7.
We developed a BDI model for surgeons considering performing reoperation after Nuss procedure. The optimal cut-off value of BDI was 8.7. This model may help surgeons to decide objectively whether corrective surgery should be performed. The main factors affecting the relationship between bar displacement and reoperation were age and preoperative HI.
Pectus excavatum; Bar displacement; Minimally invasive surgery; Complication
Developing electronics in unconventional forms provides opportunities to expand the use of electronics in diverse applications including bio-integrated or implanted electronics. One of the key challenges lies in integrating semiconductor microdevices onto unconventional substrates without glue, high pressure or temperature that may cause damage to microdevices, substrates or interfaces. This paper describes a solution based on natural gecko setal arrays that switch adhesion mechanically on and off, enabling pick and place manipulation of thin microscale semiconductor materials onto diverse surfaces including plants and insects whose surfaces are usually rough and irregular. A demonstration of functional ‘geckoprinted’ microelectronic devices provides a proof of concept of our results in practical applications.
gecko; adhesive; seta; transfer printing; flexible electronics; solar microcell
To introduce novel acquisition and post-processing approaches for susceptibility weighted imaging (SWI) to remove background field inhomogeneity artifacts in both magnitude and phase data.
The proposed method acquires three echoes in a 3D gradient echo (GRE) sequence, with a field compensation gradient (z-shim gradient) applied to the third echo. The artifacts in the magnitude data are compensated by signal estimation from all three echoes. The artifacts in phase signals are removed by modeling the background phase distortions using Gaussians. The method was applied in vivo and compared with conventional SWI.
The method successfully compensates for background field inhomogeneity artifacts in magnitude and phase images, and demonstrated improved SWI images. In particular, vessels in frontal lobe, which were not observed in conventional SWI, were identified in the proposed method.
The new method improves image quality in SWI by restoring signal in the frontal and temporal regions.
compensation gradient; field inhomogeneity induced artifac; Gaussian modeling removal; magnetic susceptibility; z-shim
Quantitative evaluation of motor functions of patients with cerebellar ataxia is vital for evidence-based treatments and has been a focus in previous investigations of movement kinematics. Due to redundancy of the musculoskeletal system, muscle activities contain more information than the movement kinematics. Therefore, it is preferable to analyze causal anomalies of muscle activities to evaluate motor functions in patients. Here we propose a new method to evaluate the motor functions at the level of muscle activities and movement kinematics. Nineteen patients and 10 control subjects performed two movement tasks of the wrist joint, a step-tracking task and a pursuit task, with a manipulandum. The movements of the wrist joint and activities of the four wrist prime movers were recorded. We developed a linear model for the wrist joint to approximate the causal relationship between muscle activities and movement kinematics in terms of the wrist joint torque. We used a canonical correlation analysis to verify the causality between the muscle activities and the movement kinematics in the model. We found that the activities of the four muscles were related almost entirely to the position and velocity, with negligible correlation with the acceleration of the wrist joint. Moreover, the ratio of the weights for position- and velocity-related torque components characterized the contents of the muscle activities in terms of the movement kinematics. Next, we compared the ratios for the two movement tasks between the controls and patients. In control subjects, the ratios indicated clear task-specific changes that conformed to the functional requirements of the tasks. In contrast, in patients, the task-specific changes diminished highly significantly. The present results indicate that this ability to accommodate motor commands to the task requirements provides a novel quantitative parameter to characterize motor functions in patients with cerebellar ataxia.
In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto’s encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias.
Cerebellar ataxias; Anti-GAD antibodies; Hashimoto’s encephalopathy; Primary autoimmune cerebellar ataxia; Gluten ataxia; Systemic lupus erythematosus; Miller Fisher syndrome; Paraneoplastic cerebellar degeneration
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)