GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults.

BACKGROUND: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. METHODS: 29 cognitively unimpaired old-aged adults (age = 70.03 ±â€¯5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression' (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. RESULTS: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. CONCLUSIONS: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD.

Laminar fMRI and computational theories of brain function.

Recently developed methods for functional MRI at the resolution of cortical layers (laminar fMRI) offer a novel window into neurophysiological mechanisms of cortical activity. Beyond physiology, laminar fMRI also offers an unprecedented opportunity to test influential theories of brain function. Specifically, hierarchical Bayesian theories of brain function, such as predictive coding, assign specific computational roles to different cortical layers. Combined with computational models, laminar fMRI offers a unique opportunity to test these proposals noninvasively in humans. This review provides a brief overview of predictive coding and related hierarchical Bayesian theories, summarises their predictions with regard to layered cortical computations, examines how these predictions could be tested by laminar fMRI, and considers methodological challenges. We conclude by discussing the potential of laminar fMRI for clinically useful computational assays of layer-specific information processing.

Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.

Stretchable coil arrays: application to knee imaging under varying flexion angles.

To fit high-density receiver arrays for MRI closely around individual target anatomies, there is a need to provide a high degree of geometric adjustability with ease of handling and patient comfort. In this work, this is accomplished by the construction of a coil array that is stretchable such that it automatically conforms to a given anatomy's shape and size. Stretchability is implemented by creating the coil conductors from braided wire mounted on an elastic textile substrate. The signal-to-noise ratio yield of such coils is measured by MRI experiments at 3 T, and the signal-to-noise ratio effect of coil stretching is investigated with and without adjustment of the matching between each coil and the respective preamplifier. Four-channel and eight-channel arrays of stretchable receiver coils are evaluated in phantoms as well as for in vivo imaging of the human knee. Exploiting stretchability, it is demonstrated that the knee can be imaged under varying flexion angles up to 60° while maintaining closely coupled array detection, high signal-to-noise ratio, and uniform coverage of the entire joint.

Realistic analytical phantoms for parallel magnetic resonance imaging.

The quantitative validation of reconstruction algorithms requires reliable data. Rasterized simulations are popular but they are tainted by an aliasing component that impacts the assessment of the performance of reconstruction. We introduce analytical simulation tools that are suited to parallel magnetic resonance imaging and allow one to build realistic phantoms. The proposed phantoms are composed of ellipses and regions with piecewise-polynomial boundaries, including spline contours, Bézier contours, and polygons. In addition, they take the channel sensitivity into account, for which we investigate two possible models. Our analytical formulations provide well-defined data in both the spatial and k-space domains. Our main contribution is the closed-form determination of the Fourier transforms that are involved. Experiments validate the proposed implementation. In a typical parallel magnetic resonance imaging reconstruction experiment, we quantify the bias in the overly optimistic results obtained with rasterized simulations-the inverse-crime situation. We provide a package that implements the different simulations and provide tools to guide the design of realistic phantoms.

A fast wavelet-based reconstruction method for magnetic resonance imaging.

In this work, we exploit the fact that wavelets can represent magnetic resonance images well, with relatively few coefficients. We use this property to improve magnetic resonance imaging (MRI) reconstructions from undersampled data with arbitrary k-space trajectories. Reconstruction is posed as an optimization problem that could be solved with the iterative shrinkage/thresholding algorithm (ISTA) which, unfortunately, converges slowly. To make the approach more practical, we propose a variant that combines recent improvements in convex optimization and that can be tuned to a given specific k-space trajectory. We present a mathematical analysis that explains the performance of the algorithms. Using simulated and in vivo data, we show that our nonlinear method is fast, as it accelerates ISTA by almost two orders of magnitude. We also show that it remains competitive with TV regularization in terms of image quality.

Noise figure characterization of preamplifiers at NMR frequencies.

A method for characterizing the noise figure of preamplifiers at NMR frequencies is presented. The noise figure of preamplifiers as used for NMR and MRI detection varies with source impedance and with the operating frequency. Therefore, to characterize a preamplifier's noise behavior, it is necessary to perform noise measurements at the targeted frequency while varying the source impedance with high accuracy. At high radiofrequencies, such impedance variation is typically achieved with transmission-line tuners, which however are not available for the relatively low range of typical NMR frequencies. To solve this issue, this work describes an alternative approach that relies on lumped-element circuits for impedance manipulation. It is shown that, using a fixed-impedance noise source and suitable ENR correction, this approach permits noise figure characterization for NMR and MRI purposes. The method is demonstrated for two preamplifiers, a generic BF998 MOSFET module and an MRI-dedicated, integrated preamplifier, which were both studied at 128MHz, i.e., at the Larmor frequency of protons at 3 Tesla. Variations in noise figure of 0.01dB or less over repeated measurements reflect high precision even for small noise figures in the order of 0.4dB. For validation, large sets of measured noise figure values are shown to be consistent with the general noise-parameter model of linear two-ports. Finally, the measured noise characteristics of the superior preamplifier are illustrated by SNR measurements in MRI data.

Mechanically adjustable coil array for wrist MRI.

In this work, the concept of mechanically adjustable MR receiver coil arrays is proposed and implemented for the specific case of human wrist imaging. An eight-channel wrist array for proton MRI at 3 Tesla was constructed and evaluated. The array adjusts to the individual anatomy by a mechanism that fits a configuration of flexible coil elements closely around the wrist. With such adjustability, it is challenging to ensure robust electrical behavior and signal-to-noise (SNR) performance. These requirements are met by preamplifier decoupling and a suitable matching strategy based on pi networks that render the coil responses robust against changes in tuning, loading and mutual coupling. The robustness of the resulting SNR yield was studied by varying the effective coil matching over a wide range in a phantom imaging experiment. While SNR variation of up to 25% was observed at the surface of the phantom the SNR was essentially constant in the critical center region. A second SNR study in wrist phantoms of different sizes confirmed the benefits of bringing the coil elements very close, up to 3 mm, to the individual target volume. These findings were supported by initial in vivo imaging, exploiting high-sensitivity detection for highly resolved structural imaging.

Diffusion-weighted imaging of the entire spinal cord.

In spite of their diagnostic potential, the poor quality of available diffusion-weighted spinal cord images often restricts clinical application to cervical regions, and improved spatial resolution is highly desirable. To address these needs, a novel technique based on the combination of two recently presented reduced field-of-view approaches is proposed, enabling high-resolution acquisition over the entire spinal cord. Field-of-view reduction is achieved by the application of non-coplanar excitation and refocusing pulses combined with outer volume suppression for removal of unwanted transition zones. The non-coplanar excitation is performed such that a gap-less volume is acquired in a dedicated interleaved slice order within two repetition times. The resulting inner volume selectivity was evaluated in vitro. In vivo diffusion tensor imaging data on the cervical, thoracic and lumbar spinal cord were acquired in transverse orientation in each of four healthy subjects. An in-plane resolution of 0.7 x 0.7 mm(2) was achieved without notable aliasing, motion or susceptibility artifacts. The measured mean +/- SD fractional anisotropy was 0.69 +/- 0.11 in the thoracic spinal cord and 0.75 +/- 0.07 and 0.63 +/- 0.08 in cervical and lumbar white matter, respectively.

Preliminary experience with visualization of intracortical fibers by focused high-resolution diffusion tensor imaging.

BACKGROUND AND PURPOSE: The inherent low anisotropy of gray matter and the lack of adequate imaging sensitivity and resolution has, so far, impeded depiction of axonal fibers to their intracortical origin or termination. We tested the hypothesis that an experimental approach with high-resolution diffusion tensor imaging (DTI) provides anisotropic data for fiber tractography with sufficient sensitivity to visualize in vivo the fine distribution of white matter bundles at the intracortical level. MATERIALS AND METHODS: We conducted phantom measurements of signal-to-noise ratio (SNR) and obtained diffusion tensor maps of the occipital lobe in 6 healthy volunteers using a dedicated miniature phased array detector at 3T. We reconstructed virtual fibers using a standard tracking algorithm. RESULTS: The coil array provided a SNR of 8.0 times higher at the head surface compared with a standard quadrature whole head coil. Diffusion tensor maps could be obtained with an in-plane resolution of 0.58 x 0.58 mm(2). The axonal trajectories reconstructed from the diffusion data penetrate into the cortical ribbon perpendicular to the pial surface. This is the expected pattern for the terminations of thalamocortical afferent fibers to the middle layers of the occipital cortex and is consistent with the known microstructural organization of the mammalian cerebral cortex. CONCLUSION: High-resolution DTI reveals intracortical anisotropy with a distinct parallel geometrical order, perpendicular to the pial surface, consistent with structures that may be identified as the terminal afferents in cortical gray matter.

Design of broadband RF pulses with polynomial-phase response.

The achievable bandwidth of common linear-phase RF pulses is limited by the maximum feasible B1 amplitude of the MR system. It has been shown previously, that this limitation can be circumvented by overlaying a quadratic phase in the frequency domain, which spreads the power across the pulse duration. Quadratic-phase RF pulses are near optimal in terms of achieving minimal B1max. In this work, it is demonstrated that further B1max reduction can be achieved by combining quadratic with higher-order polynomial-phase functions. RF pulses with a phase response up to tenth order were designed using the Shinnar-Le Roux transformation, yielding considerable increases in bandwidth and selectivity as compared to pure quadratic-phase pulses. These benefits are studied for a range of pulse specifications and demonstrated experimentally. For B1max = 20 microT and a pulse duration of 2.1 ms, it was possible to increase the bandwidth from 3.1 kHz for linear and 3.8 kHz for a quadratic to 9.9 kHz for a polynomial-phase pulse.

Reduced field-of-view MRI using outer volume suppression for spinal cord diffusion imaging.

A spin-echo single-shot echo-planar imaging (SS-EPI) technique with a reduced field of view (FOV) in the phase-encoding direction is presented that simultaneously reduces susceptibility effects and motion artifacts in diffusion-weighted (DW) imaging (DWI) of the spinal cord at a high field strength (3T). To minimize aliasing, an outer volume suppression (OVS) sequence was implemented. Effective fat suppression was achieved with the use of a slice-selection gradient-reversal technique. The OVS was optimized by numerical simulations with respect to T(1) relaxation times and B(1) variations. The optimized sequence was evaluated in vitro and in vivo. In simulations the optimized OVS showed suppression to <0.25% and approximately 3% in an optimal and worst-case scenario, respectively. In vitro measurements showed a mean residual signal of <0.95% +/- 0.42 for all suppressed areas. In vivo acquisition with 0.9 x 1.05 mm(2) in-plane resolution resulted in artifact-free images. The short imaging time of this technique makes it promising for clinical studies.

Influence of SENSE on image properties in high-resolution single-shot echo-planar DTI.

Limited spatial resolution is a key obstacle to the study of brain white matter structure with diffusion tensor imaging (DTI). In its frequent implementation with single-excitation spin-echo echo-planar sequences, DTI's ability to resolve small structures is strongly restricted by T2 and T2* decay, B0 inhomogeneity, and limited signal-to-noise ratio (SNR). In this work the influence of sensitivity encoding (SENSE) on diffusion-weighted (DW) image properties is investigated. Computer simulations showed that the PSF becomes narrower with increasing SENSE reduction factors, R, enhancing the intrinsic resolution. After a brief theoretical discussion, we describe the estimation of SNR on a pixel-by-pixel basis as a function of R. The mean image SNR behavior is manifold: SENSE is capable of increasing SNR efficiency by reducing the echo time (TE). Each SNR(R) curve reveals a maximum that depends on the amount of partial Fourier encoding used. The overall best SNR efficiency for an eight-element head coil array and a b-factor of 1000 s/mm2 is achieved at R = 2.1 and partial Fourier encoding of 60%. In vivo tensor maps of volunteers and a patient, with an in-plane resolution of 0.78 x 0.78 mm2, are also presented to demonstrate the practical implementation of the parallel approach.

SENSE-DTI at 3 T.

While holding vast potential, diffusion tensor imaging (DTI) with single-excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal-to-noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in-plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high-resolution tensor mapping is demonstrated.

Advances in sensitivity encoding with arbitrary k-space trajectories.

New, efficient reconstruction procedures are proposed for sensitivity encoding (SENSE) with arbitrary k-space trajectories. The presented methods combine gridding principles with so-called conjugate-gradient iteration. In this fashion, the bulk of the work of reconstruction can be performed by fast Fourier transform (FFT), reducing the complexity of data processing to the same order of magnitude as in conventional gridding reconstruction. Using the proposed method, SENSE becomes practical with nonstandard k-space trajectories, enabling considerable scan time reduction with respect to mere gradient encoding. This is illustrated by imaging simulations with spiral, radial, and random k-space patterns. Simulations were also used for investigating the convergence behavior of the proposed algorithm and its dependence on the factor by which gradient encoding is reduced. The in vivo feasibility of non-Cartesian SENSE imaging with iterative reconstruction is demonstrated by examples of brain and cardiac imaging using spiral trajectories. In brain imaging with six receiver coils, the number of spiral interleaves was reduced by factors ranging from 2 to 6. In cardiac real-time imaging with four coils, spiral SENSE permitted reducing the scan time per image from 112 ms to 56 ms, thus doubling the frame-rate.

Sensitivity-encoded spectroscopic imaging.

Sensitivity encoding (SENSE) offers a new, highly effective approach to reducing the acquisition time in spectroscopic imaging (SI). In contrast to conventional fast SI techniques, which accelerate k-space sampling, this method permits reducing the number of phase encoding steps in each phase encoding dimension of conventional SI. Using a coil array for data acquisition, the missing encoding information is recovered exploiting knowledge of the distinct spatial sensitivities of the individual coil elements. In this work, SENSE is applied to 2D spectroscopic imaging. Fourfold reduction of scan time is achieved at preserved spectral and spatial resolution, maintaining a reasonable SNR. The basic properties of the proposed method are demonstrated by phantom experiments. The in vivo feasibility of SENSE-SI is verified by metabolic imaging of N-acetylaspartate, creatine, and choline in the human brain. These results are compared to conventional SI, with special attention to the spatial response and the SNR.

Sensitivity encoded cardiac MRI.

Imaging speed is a key factor in most cardiovascular applications of magnetic resonance imaging. Recently, simultaneous signal acquisition with multiple coils has received increasing attention as a means of enhancing scan speed in MRI. Based on this approach, the sensitivity encoding technique SENSE enables substantial scan time reduction by exploiting the inherent spatial encoding effect of receiver coil sensitivity. This work studies the benefit of sensitivity encoding for cardiovascular MRI. SENSE is applied to accelerate common breath-hold imaging as well as real-time imaging by factors up to 3.2. In the breath-hold mode with ECG triggering, this speed benefit has been used both for reducing the breath-hold interval and for improving spatial resolution. In cardiac real-time imaging without triggering and breath control, the SENSE approach has enabled significantly enhanced temporal resolution, ranging down to 13 ms (77 frames/s). Cardiac real-time SENSE is demonstrated in several modes, including real-time imaging of three parallel slices at a rate of 25 triple frames per second.

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE).

Diffusion-weighted single-shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPI's potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion-weighted SENSE-sshEPI using different reduction factors (1.0 < or = R < or = 3.0). Additionally, a high-resolution diffusion-weighted SENSE-sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI-related image distortions were markedly diminished. Chemical shift artifacts and eddy current-induced image warping were still present, although to a markedly smaller extent. Measured direction-dependent diffusion-coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion-weighted SENSE-sshEPI in patients with subacute stroke. Because of the faster k-space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion.

Specific coil design for SENSE: a six-element cardiac array.

In sensitivity encoding (SENSE), the effects of inhomogeneous spatial sensitivity of surface coils are utilized for signal localization in addition to common Fourier encoding using magnetic field gradients. Unlike standard Fourier MRI, SENSE images exhibit an inhomogeneous noise distribution, which crucially depends on the geometrical sensitivity relations of the coils used. Thus, for optimum signal-to-noise-ratio (SNR) and noise homogeneity, specialized coil configurations are called for. In this article we study the implications of SENSE imaging for coil layout by means of simulations and imaging experiments in a phantom and in vivo. New, specific design principles are identified. For SENSE imaging, the elements of a coil array should be smaller than for common phased-array imaging. Furthermore, adjacent coil elements should not overlap. Based on the findings of initial investigations, a configuration of six coils was designed and built specifically for cardiac applications. The in vivo evaluation of this array showed a considerable SNR increase in SENSE images, as compared with a conventional array. Magn Reson Med 45:495-504, 2001.

Contrast-enhanced 3D MRA using SENSE.

Sensitivity encoding (SENSE) was used to improve the performance of three-dimensional contrast-enhanced magnetic resonance angiography (3D CE-MRA). Utilizing an array of receiver coils for sensitivity encoding, the encoding efficiency of gradient-echo imaging was increased by factors of up to three. The feasibility of the approach was demonstrated for imaging of the abdominal vasculature. On the one hand, using a SENSE reduction factor of two, the spatial resolution of a breath-hold scan of 17 seconds was improved to 1.0 x 2.0 x 2.0 mm(3). On the other hand, using threefold reduction, time-resolved 3D CE-MRA was performed with a true temporal resolution of 4 seconds, at a spatial resolution of 1.6 x 2.1 x 4.0 mm(3). CE-MRA with SENSE was performed in healthy volunteers and patients and compared with a standard protocol. Throughout, diagnostic quality images were obtained, showing the ability of sensitivity encoding to enhance spatial and/or temporal resolution considerably in clinical angiographic examinations.