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1.  The Use of Magnetic Resonance Spectroscopy in the Subacute Evaluation of Athletes Recovering from Single and Multiple Mild Traumatic Brain Injury 
Journal of Neurotrauma  2012;29(13):2297-2304.
Advanced neuroimaging techniques have shown promise in highlighting the subtle changes and nuances in mild traumatic brain injury (MTBI) even though clinical assessment has shown a return to pre-injury levels. Here we use 1H-magnetic resonance spectroscopy (1H-MRS) to evaluate the brain metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) in the corpus callosum in MTBI. Specifically, we looked at the NAA/Cho, NAA/Cr, and Cho/Cr ratios in the genu and splenium. We recruited 20 normal volunteers (NV) and 28 student athletes recovering from the subacute phase of MTBI. The MTBI group was categorized based upon the number of MTBIs and time from injury to 1H-MRS evaluation. Significant reductions in NAA/Cho and NAA/Cr ratios were seen in the genu of the corpus callosum, but not in the splenium, for MTBI subjects, regardless of the number of MTBIs. MTBI subjects recovering from their first MTBI showed the greatest alteration in NAA/Cho and NAA/Cr ratios. Time since injury to 1H-MRS acquisition was based upon symptom resolution and did not turn out to be a significant factor. We observed that as the number of MTBIs increased, so did the length of time for symptom resolution. Unexpected findings from this study are that MTBI subjects showed a trend of increasing NAA/Cho and NAA/Cr ratios that coincided with increasing number of MTBIs.
PMCID: PMC3430486  PMID: 22780855
concussion; 1H-MRS; MTBI; multiple MTBI
2.  Metabolic alterations in corpus callosum may compromise brain functional connectivity in MTBI patients: an 1H-MRS study 
Neuroscience Letters  2011;509(1):5-8.
After clinical resolution of signs and symptoms of mild traumatic brain injury (MTBI) it is still not clear if there are residual abnormalities of structural or functional brain networks. We have previously documented disrupted interhemispheric functional connectivity in “asymptomatic” concussed individuals during the sub-acute phase of injury. Testing of 15 normal volunteers (NV) and 15 subacute MTBI subjects was performed within 24 hours of clinical symptoms resolution and medical clearance for the first stage of aerobic activity. In this MRS study we report (a) both in the genu and splenium of the corpus callosum NAA/Cho and NAA/Cr ratios were significantly (p<0.05) lower in MTBI subjects shortly after the injury compared to NVs, and (b) the metabolic ratio NAA/Cho in the splenium significantly correlated with the magnitude of inter-hippocampal functional connectivity in normal volunteers, but not in MTBI. This novel finding supports our hypothesis that the functional disruption of interhemispheric brain networks in MTBI subjects results from compromised metabolic integrity of the corpus callosum and that this persists despite apparent clinical return to baseline.
PMCID: PMC3268821  PMID: 22108503
3.  Fractional Order Analysis of Sephadex Gel Structures: NMR Measurements Reflecting Anomalous Diffusion 
We report the appearance of anomalous water diffusion in hydrophilic Sephadex gels observed using pulse field gradient (PFG) nuclear magnetic resonance (NMR). The NMR diffusion data was collected using a Varian 14.1 Tesla imaging system with a home-built RF saddle coil. A fractional order analysis of the data was used to characterize heterogeneity in the gels for the dynamics of water diffusion in this restricted environment. Several recent studies of anomalous diffusion have used the stretched exponential function to model the decay of the NMR signal, i.e., exp[−(bD)α], where D is the apparent diffusion constant, b is determined the experimental conditions (gradient pulse separation, durations and strength), and α is a measure of structural complexity. In this work, we consider a different case where the spatial Laplacian in the Bloch-Torrey equation is generalized to a fractional order model of diffusivity via a complexity parameter, β, a space constant, μ, and a diffusion coefficient, D. This treatment reverts to the classical result for the integer order case. The fractional order decay model was fit to the diffusion-weighted signal attenuation for a range of b-values (0 < b < 4,000 s-mm−2). Throughout this range of b values, the parameters β, μ and D, were found to correlate with the porosity and tortuosity of the gel structure.
PMCID: PMC3144506  PMID: 21804746
diffusion; exponential; fractional derivative; fractal; magnetic resonance; Sephadex gel
4.  Faraday Shields within a Solenoidal Coil to Reduce Sample Heating: Numerical Comparison of Designs and Experimental Verification 
A comparison of methods to decrease RF power dissipation and related heating in conductive samples using passive conductors surrounding a sample in a solenoid coil is presented. Full-Maxwell finite difference time domain numerical calculations were performed to evaluate the effect of the passive conductors by calculating conservative and magnetically-induced electric field and magnetic field distributions. To validate the simulation method, experimental measurements of temperature increase were conducted using a solenoidal coil (diameter 3 mm), a saline sample (10 mM NaCl) and passive copper shielding wires (50 μm diameter). The temperature increase was 58% lower with the copper wires present for several different input powers to the coil. This was in good agreement with simulation for the same geometry, which indicated 57% lower power dissipated in the sample with conductors present. Simulations indicate that some designs should be capable of reducing temperature increase by more than 85%.
PMCID: PMC2818242  PMID: 19879784
solenoidal coil; shield; SAR; sample heating
5.  A multiscale lattice Boltzmann model of macro- to micro-scale transport, with applications to gut function 
Nutrient absorption in the small intestine cannot occur until molecules are presented to the epithelial cells that line intestinal villi, finger-like protrusions under enteric control. Using a two-dimensional multiscale lattice Boltzmann model of a lid-driven cavity flow with ‘villi’ at the lower surface, we analyse the hypothesis that muscle-induced oscillatory motions of the villi generate a controlled ‘micro-mixing layer’ (MML) that couples with the macro-scale flow to enhance absorption. Nutrient molecules are modelled as passive scalar concentrations at high Schmidt number. Molecular concentration supplied at the cavity lid is advected to the lower surface by a lid-driven macro-scale eddy. We find that micro-scale eddying motions enhance the macro-scale advective flux by creating an MML that couples with the macro-scale flow to increase absorption rate. We show that the MML is modulated by its interactions with the outer flow through a diffusion-dominated layer that separates advection-dominated macro-scale and micro-scale mixed layers. The structure and strength of the MML is sensitive to villus length and oscillation frequency. Our model suggests that the classical explanation for the existence of villi—increased absorptive surface area—is probably incorrect. The model provides support for the potential importance of villus motility in the absorptive function of the small intestine.
PMCID: PMC3263792  PMID: 20478911
gastrointestinal; intestine; gut; absorption; villi; lattice Boltzmann method
6.  Experimental and Numerical Assessment of MRI-Induced Temperature Change and SAR Distributions in Phantoms and In Vivo 
It is important to accurately characterize the heating of tissues due to the radiofrequency energy applied during MRI. This has led to an increase in the use of numerical methods to predict specific energy absorption rate distributions for safety assurance in MRI. To ensure these methods are accurate for actual MRI coils, however, it is necessary to compare to experimental results. Here, we report results of some recent efforts to experimentally map temperature change and specific energy absorption rate in a phantom and in vivo where the only source of heat is the radiofrequency fields produced by the imaging coil. Results in a phantom match numerical simulation well, and preliminary results in vivo show measurable temperature increase. With further development, similar methods may be useful for verifying numerical methods for predicting specific energy absorption rate distributions and in some cases for directly measuring temperature changes and specific energy absorption rate induced by the radiofrequency fields in MRI experiments.
PMCID: PMC2836721  PMID: 19785018
specific absorption rate; MR thermography; simulation; proton resonance frequency; MRI
7.  Brain Phenotypes in Two FGFR2 Mouse Models for Apert Syndrome 
Apert syndrome (AS) is one of at least nine disorders considered members of the fibroblast growth factor receptor (FGFR) -1, -2, and -3–related craniosynostosis syndromes. Nearly 100% of individuals diagnosed with AS carry one of two neighboring mutations on Fgfr2. The cranial phenotype associated with these two mutations includes coronal suture synostosis, either unilateral (unicoronal synostosis) or bilateral (bicoronal synostosis). Brain dysmorphology associated with AS is thought to be secondary to cranial vault or base alterations, but the variation in brain phenotypes within Apert syndrome is unexplained. Here, we present novel three-dimensional data on brain phenotypes of inbred mice at postnatal day 0 each carrying one of the two Fgfr2 mutations associated with AS. Our data suggest that the brain is primarily affected, rather than secondarily responding to skull dysmorphogenesis. Our hypothesis is that the skull and brain are both primarily affected in craniosynostosis and that shared phenogenetic developmental processes affect both tissues in craniosynostosis of Apert syndrome.
PMCID: PMC2829947  PMID: 20077479
Apert syndrome; craniosynostosis; suture; mouse; skull; brain; development
8.  Reliability and Validity of a Novel Muscle Contusion Device 
Journal of Athletic Training  2009;44(3):275-278.
Many models have been employed to replicate skeletal muscle injury associated with trauma; however, most are restricted to 1 level of severity.
To create and validate an injury-producing device that could generate multiple levels of injury severity.
Validation study.
Patients or Other Participants:
Twenty-six male Wistar rats, 3 to 4 months old.
A contusion device was developed and its ability to deliver consistent impacts was validated alone and in the presence of an experimental animal. A free-falling mass (267 g) was adjusted to the desired height (40, 50, 60, or 70 cm) and then dropped.
Main Outcome Measure(s):
Peak load, peak displacement, impulse, energy, and velocity peak were measured. Injury severity was determined using magnetic resonance imaging.
Outcome measures observed from the device alone were different by height (F18,136  =  21.807, P < .001, 1−β  =  1.0). Outcomes using the experimental animals were also dependent on height (F14,102  =  68.679, P < .001, 1−β  =  1.0). Linear regression analyses indicated that height accounted for 17% to 89% of the variance.
Mild to moderate and moderate to severe injuries can be replicated with this device, which will be useful in evaluating clinical treatments on acute muscle injury.
PMCID: PMC2681216  PMID: 19478842
blunt trauma; magnetic resonance imaging; skeletal muscle injuries

Results 1-8 (8)