Kâmil Uǧurbil

Microvascular BOLD contribution at 4 and 7 T in the human brain: Gradient-echo and spin-echo fMRI with suppression of blood effects

The BOLD signal consists of an intravascular (IV) and an extravascular (EV) component from both small and large vessels. Their relative contributions are dependent on field strength, imaging technique, and echo time. The IV and EV contributions were investigated in the human visual cortex at 4 and 7 T using spin‐echo and gradient‐echo BOLD fMRI with and without suppression of blood effects. Spin‐echo acquisition suppresses EV BOLD from large veins and reflects predominantly blood T2 changes and EV BOLD signal from small blood vessels. At a short echo time (32 ms), diffusion gradient‐based suppression of blood signals resulted in a 75% and 20% decrease in spin‐echo BOLD changes at 4 T and 7 T, respectively. However, at echo times (55–65 ms) approximating tissue T2 typically used for optimal BOLD contrast, these gradients had much smaller effects at both fields, consistent with the decreasing blood T2 with increasing field strength. Gradient‐echo BOLD percent changes, with relatively long echo times at both fields, were virtually unaffected by gradients that attenuated the blood contribution because the EV BOLD surrounding both large and small vessels dominated. These results suggest that spin‐echo BOLD fMRI at 4 and 7 T, with TE approximating tissue T2, significantly reduces nonspecific mapping signals from large vessels and significantly accentuates microvasculature contributions. Magn Reson Med 49:1019–1027, 2003.

In vivo 1H NMR spectroscopy of the human brain at 7 T

In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo‐time STEAM was used to minimize J‐modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher‐order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single‐shot spectra and from the direct detection of glucose at 5.23 ppm in 8‐ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J‐coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo‐inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment. Magn Reson Med 46:451–456, 2001.

Optimization of modulation functions to improve insensitivity of adiabatic pulses to variations in B1 magnitude

Abstract Amplitude- and frequency-modulated pulses or the equivalent amplitude- and phase-modulated pulses based on adiabatic principles achieve their transformations of magnetization vectors over a large range of variation in B1 magnitude. The B1-insensitivity of the pulses depends on the particular modulation functions employed. In this paper, we examine the factors that govern the B1 tolerance of these pulses and illustrate that previously used amplitude/frequency modulation functions sin/cos, sech/tanh, or constant/tan are far less than optimum in achieving maximal B1 insensitivity on resonance. We describe a new method by which optimized modulation functions can be constructed to impart insensitivity to B1 inhomogeneities over a predetermined B1 range. This is accomplished by dictating that the pulses based on the new modulation functions fulfill the adiabatic condition over the predetermined B1 range and for the complete duration of the pulse. The new functions also provide the additional advantage of operating at lower pulse power. Experimental and theoretical data are presented to illustrate the superiority of the new modulation functions.

31P-NMR studies of respiratory regulation in the intact myocardium

The mechanism by which mitochondrial respiration is coupled to ATP consumption in intact tissues is unclear. We determined the relationship between high‐energy phosphate levels and oxygen consumption rate in rat hearts operating over a range of workloads and perfused with different substrates. With pyruvate + glucose perfusion, ADP levels were in general very low, and varied with MVO2 yielding an apparent Km of 25 ± 5 μM, suggesting regulation of oxidative phosphorylation through availability of ADP. In contrast, with glucose perfusion in the presence or absence of insulin, ADP levels, ADP/ATP ratio or the phosphate potential were relatively constant over the workload range examined and generally not correlated with alterations in MVO2; it is suggested that under these conditions, carbon substrate delivery to the mitochondria may control mitochondrial respiration. The common feature of both of the suggested regulatory mechanisms is substrate limitation which, however, is exercised at different metabolic points depending on the carbon substrate available to the myocardium.

Amplitude- and frequency-modulated pulses to achieve 90° plane rotations with inhomogeneous B1 fields

In NMR spectroscopy inhomogeneities in B1 field profiles and problems generated by such inhomogeneities can be severe. This is particularly evident in in vivo applications and especially with surface coils (I) which are employed frequently with intact animal studies. The magnitude of the Bi field generated by a surface coil is strongly dependent on spatial coordinates. As a consequence, surface coils cannot be used for rf transmission in applications that require homogeneous BI fields such as image construction or localized spectroscopy conducted using tailored pulses in conjunction with pulsed-field gradients (2); in such applications, a “whole body” coil must be employed for rf transmission while signal detection is performed through a surface coil. In contrast, the spatial variations in the surface coil B, field provide the basis for rotating-frame localization techniques (3-6). However, even in these cases, there exist important deficiencies whose origin is the inhomogeneous Bi field profile. For example, rotating-frame techniques which rely on amplitude modulation to obtain a set of chemical-shift spectra as a function of position (4, 5) always leave some of the magnetization along the z axis; this degrades the signal-to-noise ratio of the measurement. Even in very simple applications where all the signals are detected from the “sensitive volume” of the surface coil irrespective of spatial location, nonuniform excitation due to variations in Br results in substantial signal-to-noise losses. The aforementioned problems can be minimized or even eliminated if uniform 90 and 180” rotations of spins about a well-defined axis can be performed despite the presence of B, field inhomogeneities. Recently, two frequencyand amplitude-modulated pulses have been described which rotate z magnetization to the -z axis (7) or the transverse plane of the rotating reference frame (8). One of the unique features of these pulses is their relative insensitivity to large variations in the B, field magnitude. However, these pulses cannot execute 90 or 180” plane rotations with a well-defined phase. Therefore, while they can be employed for signal excitation or inversion, they cannot be used for refocusing or rotation of magnetization vectors from the transverse plane onto the z axis. In this paper, we describe two pulses that can accomplish a 90” plane rotation in the presence of large B, field inhomogeneities. These pulses are composed of two or more segments each of which is based on the sin/cos amplitudeand frequency-mod-

Amplitude- and frequency/phase-modulated refocusing pulses that induce plane rotations even in the presence of inhomogeneous B1 fields

Amplitude- and frequency/phase-modulated 180† plane rotation pulses that can achieve both inversion and refocusing transformations in the presence of large B1 variations are presented. Such pulses are required especially in in vivo applications where some of the most commonly used coils generate highly inhomogeneous RF fields. The principles involved in constructing such pulses are discussed in detail together with five different types of problems encountered that affect performance of these pulses off resonance. The refocusing transformation is achieved by inverting the effective field halfway through the pulse. The different pulses discussed tolerate very large and similar range of variations in B1 magnitude on resonance, but behave differently off resonance. Two of the pulses achieve 180† plane rotations with constant phase over a useful off resonance range and in the presence of large B1 variations. Therefore, these pulses are expected to be useful in high-resolution as well as in vivo NMR applications.

Magnetization-transfer measurements of individual rate constants in the presence of multiple reactions

Abstract Magnetization-transfer techniques, such as saturation or inversion transfer, are extremely useful methods for measuring chemical-exchange rate constants which are comparable to spin-lattice relaxation rate constants of the exchanging spins. Although such determinations are relatively simple for a two-site exchange case, complications arise when multisite exchanges are involved. This severely restricts the applicability of this type of measurement, especially in whole cells and tissues where many reactants are utilized by more than one enzyme. In this paper, it is shown that a multisite exchange problem can first be reduced effectively to a two-site exchange, and a single rate constant can subsequently be measured simply and unequivocally. Application of this procedure to equilibrium and nonequilibrium chemical-exchange problems are discussed.

Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems†

Proton‐observed carbon‐edited (POCE) NMR spectroscopy is commonly used to measure 13C labeling with higher sensitivity compared to direct 13C NMR spectroscopy, at the expense of spectral resolution. For weakly coupled first‐order spin systems, the multiplet signal at a specific proton chemical shift in POCE spectra directly reflects 13C enrichment of the carbon attached to this proton. The present study demonstrates that this is not necessarily the case for strongly coupled second‐order spin systems. In such cases NMR signals can be detected in the POCE spectra even at chemical shifts corresponding to protons bound to 12C. This effect is demonstrated theoretically with density matrix calculations and simulations, and experimentally with measured POCE spectra of [3‐13C]glutamate. Magn Reson Med, 2006.

Fourier series windows on and off resonance using multiple coils and longitudinal modulation and longitudinal modulation

Abstract Descriptions of Fourier series windows (FSWs) using multiple coils for in vivo NMR spectroscopy are presented. Spatially dependent phase shifts in experiments implemented with separate transmitter and receiver coils are shown to exist and are theoretically analyzed on and off resonance. With computer simulations, we illustrate the occurrence of unwanted dispersive signals in such experiments. A new approach to the FSW experiment is introduced in which the magnetization is longitudinally modulated and dispersive signals are not produced in experiments executed with multiple transmitter coils. In addition, the longitudinally modulated FSWs avoid localization artifacts due to off resonance excitation within a reasonable chemical-shift range for in vivo 31P spectroscopy.

Application of parallel imaging to fMRI at 7 tesla utilizing a high 1D reduction factor

Gradient‐echo EPI, blood oxygenation level‐dependent (BOLD) functional MRI (fMRI) using parallel imaging (PI) is demonstrated at 7 Tesla with 16 channels, a fourfold 1D reduction factor (R), and fourfold maximal aliasing. The resultant activation detection in finger‐tapping fMRI studies was robust, in full agreement with expected activation patterns based on prior knowledge, and with functional maps generated from full field of view (FOV) coverage of k‐space using segmented acquisition. In all aspects the functional maps acquired with PI outperformed segmented coverage of full k‐space. With a 1D R of 4, fMRI activation based on PI had higher statistical significance, up to 1.6‐fold in an individual case and 1.25 ± .25 (SD) fold when averaged over six studies, compared to four‐segment/full‐FOV data in which the reduction in the image signal‐to‐noise ratio (SNR) due to k‐space undersampling was compensated for by acquiring additional repetitions of the undersampled k‐space. When this compensation for loss in SNR was not performed, the effect of PI was determined by the ratio of physiologically induced vs. intrinsic (thermal) noise in the fMRI time series and the extent to which physiological “noise” was amplified by the use of segmentation in the full‐FOV data. The results demonstrate that PI is particularly beneficial at this ultrahigh field strength, where both the intrinsic image SNR and temporal signal fluctuations due to physiological processes are large. Magn Reson Med, 2006.