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1.  MRI and Localized Proton Spectroscopy in Human Leg Muscle at 7 Tesla Using Longitudinal Traveling Waves 
Using a small resonant loop to produce a longitudinal traveling wave on a human 7-T system allows MR to be performed over the entire volume of the human leg. We have used this capability to perform localized proton MR spectroscopy of the lipid composition of muscle in volunteers with a coil placed ~30 cm away from the region of interest. Spectra with a reasonable signal-to-noise ratio can be acquired in a clinically relevant data acquisition time of less than 5 min using the loop in transmit/receive mode, maintaining the full flexibility to acquire spectra from any part of the calf and/or thigh. If a local receive coil is used in combination with the remote transmit coil, then the signal-to-noise improves significantly, as expected.
PMCID: PMC2846515  PMID: 20099323
remote transmission; traveling waves; muscle spectroscopy; intracellular and extracellular lipids; high field imaging
3.  A Computational Study of the Hydrodynamics in the Nasal Region of a Hammerhead Shark (Sphyrna tudes): Implications for Olfaction 
PLoS ONE  2013;8(3):e59783.
The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory chambers, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Computed external flow patterns elucidate the occurrence of flow phenomena that result in high and low pressures at the incurrent and excurrent nostrils, respectively, which induces flow through the olfactory chamber. The major (prenarial) nasal groove along the cephalofoil is shown to facilitate sampling of a large spatial extent (i.e., an extended hydrodynamic “reach”) by directing oncoming flow towards the incurrent nostril. Further, both the major and minor nasal grooves redirect some flow away from the incurrent nostril, thereby limiting the amount of fluid that enters the olfactory chamber. Internal hydrodynamic flow patterns are also revealed, where we show that flow rates within the sensory channels between olfactory lamellae are passively regulated by the apical gap, which functions as a partial bypass for flow in the olfactory chamber. Consequently, the hammerhead shark appears to utilize external (major and minor nasal grooves) and internal (apical gap) flow regulation mechanisms to limit water flow between the olfactory lamellae, thus protecting these delicate structures from otherwise high flow rates incurred by sampling a larger area.
PMCID: PMC3612105  PMID: 23555780
4.  In Vivo Determination of Human Breast Fat Composition by 1H MRS at 7T 
The role of diet and fat consumption in the pathogenesis of breast cancer is an important subject. We report on a method for non-invasive determination of lipid composition in human breast by proton MRS at 7T. Two respiratory-triggered TE-averaged STEAMs were performed on the adipose tissue of ten healthy volunteers where the second acquisition had all gradients inverted. This acquisition protocol allows for suppression of modulation side bands that complicate spectral analysis at the short TEavg = 24.5 ms used. The entire acquisition takes approximately 10 minutes. Ten lipid peaks were typically resolved. T1 and T2 were also measured and used to correct the peak intensities. The average lipid composition calculated was saturated 28.7 ± 8.4%, monounsaturated 48.5 ± 7.9 %, and polyunsaturated 22.7 ± 3.1%, in close agreement with reported values from subcutaneous adipose measurements. Intra-subject variability was 2.0, 1.6, and 3.6% for the saturated, monounsaturated, and polyunsaturated fractions, respectively. In conclusion, we have shown that a chemical analysis of lipids in breast tissue can be determined quite simply, quickly, and non-invasively by proton MRS at 7T.
PMCID: PMC3245342  PMID: 21656551
adipose; NMR; MUFA; PUFA; TE-average; triglycerides
5.  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
6.  Feasibility of pseudocontinuous arterial spin labeling at 7 T with whole-brain coverage 
Magma (New York, N.y.)  2011;25(2):83-93.
We studied the feasibility of pseudocontinuous arterial spin labeling (pCASL) at 7 T.
Materials and methods
Simulations were performed to find the optimal labeling parameters for pCASL, with particular attention to the maximum-allowed specific absorption rate (SAR). Subsequently, pCASL experiments (four volunteers) were performed to find the B1 efficiency at the labeling position with and without high-permittivity pads placed around the head, and to study the optimal labeling duration (four separate volunteers). Finally, feasibility of whole-brain pCASL imaging was tested.
Simulations showed that a lower B1 efficiency should be compensated by a lower effective flip angle of the labeling, a moderately shorter labeling duration, and a longer repetition time. B1 efficiency in the internal carotid arteries just below the carotid siphon was approximately 55% and 35% with and without high-permittivity pads, respectively. In vivo experiments showed an optimal labeling duration of 1,500 ms, although longer labeling durations up to 2,500 ms resulted in similar signal-to-noise efficiency. Whole-brain pCASL imaging was demonstrated in a single volunteer.
Despite decreased B1 efficiency, sufficient labeling efficiency can be achieved for whole-brain pCASL at 7 T with high-permittivity pads. However, image quality is still limited compared with 3 T, probably due to imaging instabilities, and further research is needed to elucidate this.
PMCID: PMC3313026  PMID: 22200964
Cerebral blood flow; MRI; Cerebral arteries; Arterial spin labeling
7.  Methodology development for simultaneous diffuse optical tomography and magnetic resonance imaging in functional human brain mapping 
We present an integrated methodology for human brain mapping by simultaneous BOLD fMRI and NIR imaging. This methodology consists of three innovative components: the construction of MRI-compatible optical probes that can be affixed to any part of the human head inside a standard MRI head-coil with minimal MR image distortion, the accurate determination of optode positions on the head from MR images, and the application of a perturbation approach and Monte Carlo method to compute the integral kernel of the Born solution to the diffusion equation for baseline optical properties. This integrated approach has been used to demonstrate promising capabilities for studying functional hemodynamic activation in human visual cortex by simultaneous fMRI and NIR tomography.
PMCID: PMC3143038  PMID: 21796235
fMRI; near-infrared tomography; diffuse optical tomography; functional imaging; human brain; visual cortex; hemodynamic response
8.  The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans 
The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show interesting spatial differences.
PMCID: PMC3138137  PMID: 21776185
near-infrared; diffuse optical tomography; fMRI; functional imaging; human brain; visual cortex; hemodynamic response; neuronal response
9.  Group Analysis of FMRI and NIR Data Simultaneously Acquired During Visual Stimulation in Humans 
We use our new combined functional near infrared spectro-imaging (fNIRSI) and magnetic resonance imaging (MRJ) technique to compare fMRI and fNIRSI data at different activation conditions, to obtain new information about the underlying physiology of the blood oxygen level dependent (BOLD) signal used in fMRI, and to assess statistical characteristics of spatial functional information provided by the group analysis of fNIRSI data. To achieve these goals we have acquired simultaneously fNIRSI and fMRI data during the presentation of the checkerboard reversing with different frequencies, and analyzed these data following the standard correlation and group analysis of variance pathway used in functional neuroimaging. . We have found that while the time courses of oxy-, deoxy-, and total- hemoglobin responses are equally well correlated with the time course of the BOLD response, the spatial pattern and magnitude of the BOLD response is better related to those of the oxy-, and total- hemoglobin responses rather than to the deoxyhemoglobin response. The statistical significance of the fNIRSI group maps is inferior to that of fMRI, and can be particularly compromised by the anatomical features of subjects.
PMCID: PMC3138475  PMID: 21776186
fMRI; imaging; human brain; photon migration
10.  Near-infrared study of the underlying physiology of the functional magnetic resonance signal in humans during hypoxia 
We use near-infrared spectroscopy to investigate hemodynamic changes in humans during a breath holding exercise and their influence on the BOLD fMRI signal. We have quantitatively compared the BOLD fMRI signals with the hemoglobin concentration changes using correlation analysis of NIRS and fMRI data.
PMCID: PMC3137896  PMID: 21769244
human brain; hypoxia; near-infrared spectroscopy; functional magnetic resonance imaging
11.  Spatial and temporal hemodynamic study of human primary visual cortex using simultaneous functional MRI and diffuse optical tomography 
The blood oxygenation level dependent (BOLD) functional MRI and near infrared optical tomography have been widely used to investigate the hemodynamic response to functional stimulation in the human brain. In this paper, we present a complete methodology of integrating the two imaging modalities to study the underlying physiological mechanism of hemodynamic response in the human primary visual cortex. The integration was made feasible thanks to the development of an MRI-compatible optical probe. The optical imaging was conducted using a frequency-domain near infrared spectrometer. The 3-dimentional optical image reconstruction was based on diffuse optical tomography (DOT) using the perturbative approach. The sensitivity function of the forward problem was obtained using Monte Carlo method. From our preliminary observation, the spatial activation pattern of deoxyhemoglobin is consistent with the BOLD signal map. The patterns of oxy- and deoxyhemoglobin are very similar. The temporal hemodynamic response shows an increased total hemoglobin concentration, which indicates an increment of cerebral blood volume (CBV) during physiological activation.
PMCID: PMC3130336  PMID: 17282286
12.  Signal and image processing techniques for functional near-infrared imaging of the human brain 
Near-infrared spectro-imaging (NIRSI) is a quickly developing method for the in-vivo imaging of biological tissues. In particular, it is now extensively employed for imaging the human brain. In this non-invasive technique, the information about the brain is obtained from the analysis of spatial light bundles formed by the photons traveling from light sources to detectors placed on the surface of the head. Most significant problems in the functional brain NIRSI are the separation of the brain information from the physiological noise in non-cerebral tissues, and the localization of functional signals. In this paper we describe signal and image processing techniques we developed in order to measure two types of functional cerebral signals: the hemodynamic responses, and neuronal responses.
PMCID: PMC3129607  PMID: 21738383
brain; MRI; near-infrared; functional imaging
13.  Localization of Asymmetric Brain Function in Emotion and Depression 
Psychophysiology  2010;47(3):442-454.
Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.
PMCID: PMC3086589  PMID: 20070577
14.  An integrated measurement system for simultaneous functional magnetic resonance imaging and diffuse optical tomography in human brain mapping 
The Review of scientific instruments  2006;77(11):114301-114301-8.
An integrated measurement system is described for performing simultaneous functional magnetic resonance imaging (fMRI) and diffuse optical tomography (DOT) for human brain mapping experiments. The components of this system consist of an MRI-compatible multi-overlapping-channel optical probe, methods for co-registration of optical and fMRI measurements, and DOT reconstruction algorithms with structural and physiological constraints derived from the MRI data. The optical probe is fully MRI-compatible in the sense that it produces negligible MR image distortion and does not require any modification to the MRI scanner or data acquisition protocol. The probe can be attached to any part of the head without posing any limitation on optical data acquisition. Co-registration of images from fMRI and optical measurements was achieved by localizing the positions of the optical fibers using MRI markers. Human studies show successful implementation of the entire system.
PMCID: PMC3051269  PMID: 21399741
15.  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
16.  A Method to Separate Conservative and Magnetically-Induced Electric Fields in Calculations for MRI and MRS in Electrically-small Samples 
This work presents a method to separately analyze the conservative electric fields (Ec, primarily originating with the scalar electric potential in the coil winding), and the magnetically-induced electric fields (Ei, caused by the time-varying magnetic field B1) within samples that are much smaller than one wavelength at the frequency of interest. The method consists of first using a numerical simulation method to calculate the total electric field (Et) and conduction currents (J) in the problem region, then calculating Ei based on J, and finally calculating Ec by subtracting Ei from Et. The method was applied to calculate electric fields for a small cylindrical sample in a solenoid at 600 MHz. When a non-conductive sample was modeled, calculated values of Ei and Ec were at least in rough agreement with very simple analytical approximations. When the sample was given dielectric and/or conductive properties, Ec was seen to decrease, but still remained much larger than Ei. When a recently-published approach to reduce heating by placing a passive conductor in the shape of a slotted cylinder between the coil and sample was modeled, reduced Ec and improved B1 homogeneity within the sample resulted, in agreement with the published results. (196 words)
PMCID: PMC2722947  PMID: 19520593
conservative electric field; magnetically induced electric field; solenoidal coil
17.  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
18.  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
19.  Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain 
Optics express  2005;13(14):5513-5521.
A complete methodology has been developed to integrate simultaneous diffuse optical tomography (DOT) and functional magnetic resonance imaging (MRI) measurements. This includes development of an MRI-compatible optical probe and a method for accurate estimation of the positions of the source and detector optodes in the presence of subject-specific geometric deformations of the optical probe. Subject-specific head models are generated by segmentation of structural MR images. DOT image reconstruction involves solution of the forward problem of light transport in the head using Monte Carlo simulations, and inversion of the linearized problem for small perturbations of the absorption coefficient. Initial results show good co-localization between the DOT images of changes in oxy- and deoxyhemoglobin concentration and functional MRI data.
PMCID: PMC2755505  PMID: 19498547
20.  Magnetic Resonance Microimaging and Numerical Simulations of Velocity Fields Inside Enlarged Flow Cells Used for Coupled NMR Microseparations 
Analytical chemistry  2005;77(5):1338-1344.
The coupling of various chemical microseparation methods with small-scale NMR detection is a growing area in analytical chemistry. The formation of enlarged flow cells within the active volume of the NMR detector can significantly increase the coil filling factor and hence the signal-to-noise ratio of the NMR spectra. However, flow cells can also lead to deterioration of the separation efficiency due to the development of complex flow patterns, the form of which depend on the particular geometry of the flow cell and the flow rate used. In this study, we investigated the flow characteristics in different flow cell geometries relevant to the coupling of capillary liquid chromatography and NMR. Computational fluid dynamics was used to simulate fluid flow inside flow cells with a volume of ~ 1 µL. Magnetic resonance microimaging was used to measure experimentally the velocity fields inside these flow cells. The results showed good agreement between experiment and simulation and demonstrated that a relatively gradual expansion and contraction is necessary to avoid areas of weak recirculation and strong radial velocities, both of which can potentially compromise separation efficiency.
PMCID: PMC2754838  PMID: 15732916
21.  A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex 
NeuroImage  2006;34(3):1136-1148.
Functional near infrared spectro-imaging (fNIRSI) is potentially a very useful technique for obtaining information about the underlying physiology of the blood oxygenation level dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). In this paper the temporal and spatial statistical characteristics of fNIRSI data are compared to those of simultaneously acquired fMRI data in the human visual cortex during a variable-frequency reversing checkerboard activation paradigm. Changes in the size of activated volume caused by changes in checkerboard reversal frequency allowed a comparison of the behavior of the spatial responses measured by the two imaging methods. fNIRSI and fMRI data were each analyzed using standard correlation and fixed-effect group analyses of variance pathways. The statistical significance of fNIRSI data was found to be much lower than that of the fMRI data, due mainly to the low signal-to-noise of the measurements. Reconstructed images also showed that, while the time-course of changes in the oxy-, deoxy-, and total hemoglobin concentrations all exhibit high correlation with that of the BOLD response, the changes in the volume of tissue measured as “activated” by the BOLD response demonstrate a closer similarity to the corresponding changes in the oxy- and total hemoglobin concentrations than to that of the deoxyhemoglobin.
PMCID: PMC2752293  PMID: 17134913
Human brain; Functional activity; Near infrared imaging; fMRI

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