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ABSTRACT: T(2)*-weighted gradient-echo MRI images at high field (≥ 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts.
NeuroImage 10/2011; 59(4):3967-75. · 5.89 Impact Factor
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ABSTRACT: Recent high-field MRI studies based on resonance frequency contrast have revealed brain structure with unprecedented detail. Although subtle magnetic susceptibility variations caused by iron and myelin seem to be important to this contrast, recent research on protein solutions suggests that chemical exchange between water and macromolecular protons may contribute substantially to the observed gray-white matter frequency contrast. To investigate this, we performed spectroscopic MRI experiments at 14 T on samples of fixed human visual cortex and fresh pig brain. To allow direct observation of any exchange-induced frequency shifts, these samples were soaked in reference chemicals (TSP and dioxane) that are assumed not to be involved in exchange. For both fresh and fixed tissues and with both reference chemicals, substantial negative exchange-induced gray-white matter frequency contrast (-6.3 to -13.5 ppb) was found, whereas intracortical contrast was negligible. The sign of the gray-white matter exchange-induced frequency difference was opposite to the overall gray-white matter frequency difference observed in vivo. This suggests that exchange contributes to, but is not sufficient to explain, the frequency contrast in vivo and tissue susceptibility differences may have a greater contribution than previously thought. The exchange-dependent contribution may report on tissue chemical composition and pH.
Magnetic Resonance in Medicine 10/2010; 65(1):35-43. · 2.96 Impact Factor
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ABSTRACT: Recent advances in high-field (>or=7 T) MRI have made it possible to study the fine structure of the human brain at the level of fiber bundles and cortical layers. In particular, techniques aimed at detecting MRI resonance frequency shifts originating from local variation in magnetic susceptibility and other sources have greatly improved the visualization of these structures. A recent theoretical study [He X, Yablonskiy DA (2009) Proc Natl Acad Sci USA 106:13558-13563] suggests that MRI resonance frequency may report not only on tissue composition, but also on microscopic compartmentalization of susceptibility inclusions and their orientation relative to the magnetic field. The proposed sensitivity to tissue structure may greatly expand the information available with conventional MRI techniques. To investigate this possibility, we studied postmortem tissue samples from human corpus callosum with an experimental design that allowed separation of microstructural effects from confounding macrostructural effects. The results show that MRI resonance frequency does depend on microstructural orientation. Furthermore, the spatial distribution of the resonance frequency shift suggests an origin related to anisotropic susceptibility effects rather than microscopic compartmentalization. This anisotropy, which has been shown to depend on molecular ordering, may provide valuable information about tissue molecular structure.
Proceedings of the National Academy of Sciences 03/2010; 107(11):5130-5. · 9.68 Impact Factor
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Masaki Fukunaga,
Tie-Qiang Li,
Peter van Gelderen,
Jacco A de Zwart, Karin Shmueli,
Bing Yao,
Jongho Lee,
Dragan Maric,
Maria A Aronova,
Guofeng Zhang,
Richard D Leapman,
John F Schenck,
Hellmut Merkle,
Jeff H Duyn
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ABSTRACT: Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region's myeloarchitecture and forms the dominant source of the observed MRI contrast.
Proceedings of the National Academy of Sciences 02/2010; 107(8):3834-9. · 9.68 Impact Factor
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ABSTRACT: Phase images in susceptibility-weighted MRI of brain provide excellent contrast. However, the phase is affected by tissue geometry and orientation relative to the main magnetic field (B(0)), and phase changes extend beyond areas of altered susceptibility. Magnetic susceptibility, on the other hand, is an intrinsic tissue property, closely reflecting tissue composition. Therefore, recently developed inverse Fourier-based methods were applied to calculate susceptibility maps from high-resolution phase images acquired at a single orientation at 7 T in the human brain (in vivo and fixed) and at 11.7 T in fixed marmoset brain. In susceptibility images, the contrast of cortical layers was more consistent than in phase images and was independent of the structures' orientation relative to B(0). The contrast of iron-rich deep-brain structures (red nucleus and substantia nigra) in susceptibility images agreed more closely with iron-dominated R(2) (*) images than the phase image contrast, which extended outside the structures. The mean susceptibility in these regions was significantly correlated with their estimated iron content. Susceptibility maps calculated using this method overcome the orientation-dependence and non-locality of phase image contrast and seem to reflect underlying tissue composition. Susceptibility images should be easier to interpret than phase images and could improve our understanding of the sources of susceptibility contrast.
Magnetic Resonance in Medicine 10/2009; 62(6):1510-22. · 2.96 Impact Factor
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ABSTRACT: Signal fluctuations in functional magnetic resonance imaging (fMRI) can result from a number of sources that may have a neuronal, physiologic or instrumental origin. To determine the relative contribution of these sources, we recorded physiological (respiration and cardiac) signals simultaneously with fMRI in human volunteers at rest with their eyes closed. State-of-the-art technology was used including high magnetic field (7 T), a multichannel detector array and high-resolution (3 mm(3)) echo-planar imaging. We investigated the relative contribution of thermal noise and other sources of variance to the observed fMRI signal fluctuations both in the visual cortex and in the whole brain gray matter. The following sources of variance were evaluated separately: low-frequency drifts due to scanner instability, effects correlated with respiratory and cardiac cycles, effects due to variability in the respiratory flow rate and cardiac rate, and other sources, tentatively attributed to spontaneous neuronal activity. We found that low-frequency drifts are the most significant source of fMRI signal fluctuations (3.0% signal change in the visual cortex, TE=32 ms), followed by spontaneous neuronal activity (2.9%), thermal noise (2.1%), effects due to variability in physiological rates (respiration 0.9%, heartbeat 0.9%), and correlated with physiological cycles (0.6%). We suggest the selection and use of four lagged physiological noise regressors as an effective model to explain the variance related to fluctuations in the rates of respiration volume change and cardiac pulsation. Our results also indicate that, compared to the whole brain gray matter, the visual cortex has higher sensitivity to changes in both the rate of respiration and the spontaneous resting-state activity. Under the conditions of this study, spontaneous neuronal activity is one of the major contributors to the measured fMRI signal fluctuations, increasing almost twofold relative to earlier experiments under similar conditions at 3 T.
Magnetic Resonance Imaging 05/2009; 27(8):1019-29. · 1.99 Impact Factor
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ABSTRACT: Heart rate fluctuations occur in the low-frequency range (<0.1 Hz) probed in functional magnetic resonance imaging (fMRI) studies of resting-state functional connectivity and most fMRI block paradigms and may be related to low-frequency blood-oxygenation-level-dependent (BOLD) signal fluctuations. To investigate this hypothesis, temporal correlations between cardiac rate and resting-state fMRI signal timecourses were assessed at 3 T. Resting-state BOLD fMRI and accompanying physiological data were acquired and analyzed using cross-correlation and regression. Time-shifted cardiac rate timecourses were included as regressors in addition to established physiological regressors (RETROICOR (Glover, G.H., Li, T.Q., Ress, D., 2000. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med 44, 162-167) and respiration volume per unit time (Birn, R.M., Diamond, J.B., Smith, M.A., Bandettini, P.A., 2006b. Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. NeuroImage 31, 1536-1548). Significant correlations between the cardiac rate and BOLD signal timecourses were revealed, particularly negative correlations in gray matter at time shifts of 6-12 s and positive correlations at time shifts of 30-42 s (TR=6 s). Regressors consisting of cardiac rate timecourses shifted by delays of between 0 and 24 s explained an additional 1% of the BOLD signal variance on average over the whole brain across 9 subjects, a similar additional variance to that explained by respiration volume per unit time and RETROICOR regressors, even when used in combination with these other physiological regressors. This suggests that including such time-shifted cardiac rate regressors will be beneficial for explaining physiological noise variance and will thereby improve the statistical power in future task-based and resting-state fMRI studies.
NeuroImage 11/2007; 38(2):306-20. · 5.89 Impact Factor
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ABSTRACT: To design and construct an anthropomorphic head phantom using materials of appropriate magnetic susceptibility and air spaces of realistic dimensions, with the aim of reproducing the susceptibility artifacts found in the human brain.
The phantom is based on a plastic skull filled with MnCl2-doped water. Materials to mimic soft tissue (wax) and bone (plastic skull) were chosen based on mass susceptibility measurements using a superconducting quantum interference device (SQUID) magnetometer. The phantom was designed for and evaluated at 4.7T using field mapping and echo-planar imaging (EPI).
The main magnetic field (B0) maps of the phantom resemble those of four volunteers' brains and have similar standard deviations (SDs). Maps of the B0 field gradients in the phantom and real brains are also similar. The phantom has relaxation times close to those of brain tissue at 4.7T. Gradient-echo (GE)-EPI images of the phantom suffer from susceptibility artifacts comparable to those in real heads and at anatomically realistic locations.
The phantom is a useful tool for evaluating and comparing different susceptibility artifact reduction techniques. The phantom could also be used to test CT-MRI coregistration in the presence of susceptibility artifacts since the water-filled brain cavity is both CT- and MR-visible.
Journal of Magnetic Resonance Imaging 08/2007; 26(1):202-7. · 2.70 Impact Factor
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ABSTRACT: Magnetic susceptibility provides an important contrast mechanism for MRI. Increasingly, susceptibility-based contrast is being exploited to investigate brain tissue microstructure and to detect abnormal levels of brain iron as these have been implicated in a variety of neuro-degenerative diseases. However, it remains unclear to what extent magnetic susceptibility-related contrast at high field relates to actual brain iron concentrations. In this study, we performed susceptibility weighted imaging as a function of field strength on healthy brains in vivo and post-mortem brain tissues at 1.5 T, 3 T and 7 T. Iron histology was performed on the tissue samples for comparison. The calculated susceptibility-related parameters R2⁎ and signal frequency shift in four iron-rich regions (putamen, globus pallidus, caudate, and thalamus) showed an almost linear dependence (r ≥ 0.90 for R2⁎; r ≥ 0.83 for phase, p < 0.01) on field strength, suggesting that potential ferritin saturation effects are not relevant to susceptibility-weighted contrast for field strengths up to 7 T. The R2⁎ dependence on the putative (literature-based) iron concentration was 0.048 Hz/T/ppm. The histological data from brain samples confirmed the linear dependence of R2⁎ on field strength and showed a slope against iron concentration of 0.0099 Hz/T/ppm dry-weight, which is equivalent to 0.05 Hz/T/ppm wet-weight and closely matched the calculated value in vivo. These results confirm the validity of using susceptibility-weighted contrast as an indicator of iron content in iron-rich brain regions. The absence of saturation effects opens the way to exploit the benefits of MRI at high field strengths for the detection of iron distributions with high sensitivity and resolution.
NeuroImage.
