Multi-slice perfusion-based functional magnetic resonance imaging (p-fMRI) is demonstrated with a color–word Stroop task as an established cognitive paradigm. Continuous arterial spin labeling (CASL) of the blood in the left common carotid artery was applied for all repetitions of the functional run in a quasi-continuous fashion, i.e., it was interrupted only during image acquisition. For comparison, blood oxygen level dependent (BOLD) contrast was detected using conventional gradient-recalled echo (GE) echo planar imaging (EPI). Positive activations in BOLD imaging appeared in p-fMRI as negative signal changes corresponding to an enhanced transport of inverted water spins into the region of interest, i.e., increased cerebral blood flow (CBF). Regional differences between the localization of activations and the sensitivity of p-fMRI and BOLD-fMRI were observed as, for example, in the inferior frontal sulcus and in the intraparietal sulcus. Quantification of CBF changes during cognitive task activation was performed on a multi-subject basis and yielded CBF increases of the order of 20–30%.

A case of subacute sclerosing panencephalitis in a 27-year-old man was serially evaluated with proton magnetic resonance spectroscopy. Metabolic abnormalities included decreased N-acetylaspartate and elevated choline and myo-inositol in a lesion visible on magnetic resonance imaging and in normal-appearing white matter. Lactate appeared increased within the lesion. Metabolic impairment was persistent after intrathecal interferon-α treatment. Spectroscopy pointing to ongoing inflammation, gliosis, and possible membrane turnover was more sensitive than imaging in detecting widespread pathology within the white matter.

Functional magnetic resonance imaging (fMRI) based on the selection of intermolecular double-quantum coherences (iDQC) was performed with a standard birdcage coil at 3 T in a group of normal human volunteers. Suppression of spurious signal contributions from unwanted coherence-transfer pathways was achieved by combining a two-step phase cycle and a long repetition time of 5 s. A gradient-recalled echo iDQC sequence (echo time, T(E) = 80 ms) yielded robust activation with a visual paradigm. Maximum z-scores were about half of those observed with conventional blood-oxygen level dependent fMRI, whereas the functional signal change increased by more than a factor of 5. No activation was obtained with a spin-echo iDQC sequence (T(E) = 160 ms), in which dephasing accumulated during the evolution period was fully rephased by an appropriate delay time. It is hypothesized that substantial inherent diffusion weighting of the iDQC technique efficiently suppresses intravascular contributions to the functional contrast. A consistent quantitative explanation of the observed amount of signal change currently remains speculative.

Spatiotemporally structured noise, such as physiological noise, is a potential source of artifacts in functional magnetic resonance imaging (fMRI) and is the main limiting factor for the detection of small blood oxygen level-dependent (BOLD) signal variations. fMRI was employed to detect low-frequency BOLD signal fluctuations. which are thought to be related to spontaneous neuronal activity in the resting human brain. The sensitivity to noise, that is, signal variations of nonBOLD origin, was investigated for two- (2D) and three-dimensional (3D) imaging techniques. Incomplete relaxation between subsequent scans increases the level of temporally and spatially correlated signal variations originating from physiological and/or systemic noise. Although inflow effects are suspected to be reduced in 3D echo-planar imaging (EPI) compared with multi-slice 2D EPI, the noise level was higher in the 3D technique. The noise level in 3D fMRI experiments was significantly increased by instabilities of the transverse steady-state magnetization as the repetition time was of the order of T-2. By implementing radiofrequency spoiling, temporal signal fluctuations and erroneous inter-regional correlation in connectivity maps were diminished to a level present in data sets acquired with 2D EPI. Copyright (c) 2005 John Wiley & Sons, Ltd.

We describe the further development of a circularly polarized helmet coil for magnetic resonance imaging (MRI) of the human brain at 3 T. The coil is used in transmit and receive (transceive) mode, a useful alternative over commercially available quadrature headcoils with scanners where phased arrays are unavailable. The coil is simple to build. Its structure is based on an assembly of two coplanar dual-loop coils of the split-circle design, which are arranged in crossed fashion. Both coils circumscribe dome-like the human head. Because of the symmetry of the assembly, a high degree of circularly polarized radiofrequency (RF) is obtained within the brain. Bench and in situ measurements of the RF magnetic field, B1, indicated good axial homogeneity and a moderate gradient along the symmetry axis. Compared to a commercial birdcage coil, the signal-to-noise ratio was increased up to a factor of 1.7 as a result of its superior filling factor. Initial applications in healthy volunteers included anatomical MRI and functional imaging with a cognitive paradigm. © 2005 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 27B: 64–74, 2005.

In a recent series of studies (see, for example, Stroman et al. Magn Reson Imag 2001; 19:827–831), an increase of water proton density has been suggested to correlate with neuronal activity. Owing to the significant implications of such a mechanism for other functional experiments, the functional signal changes in humans at very short echo times were re‐examined by spin‐echo EPI at 3 T. The results do not confirm the previous hypothesis of a significant increase in extravascular proton density at TE = 0. Instead, an alternative explanation of the effect is offered: The use of a low threshold to identify activated voxels may generate an artificial offset in functional contrast due to the inclusion of false‐positives in the analysis. Magn Reson Med 53:470–473, 2005. © 2005 Wiley‐Liss, Inc.

In evaluating the sensitivity of arterial spin labeling (CASL) and for quantification of perfusion, knowledge of the transit time from the labeling plane to the imaging slice is crucial. The purpose of the current study was to obtain estimates of transit times relevant under the specific experimental conditions of CASL in human subjects using a separate local labeling coil at the neck. Specifically, the post-label delay (PLD), i.e. the time between the end of the labeling period and the image acquisition, was varied either with or without additional application of crusher gradients to suppress intravascular signal contributions. The overall sensitivity change for varying the PLD between 1000 and 1700 ms was low. A tissue transit time from the neck to an axial supraventricular section through Broca's knee was obtained by fitting the PLD dependence to a two-compartment model. Averaging over subjects yielded 1930 +/- 10 ms for the tissue transit time, and 73 +/- 5 ml min(-1) 100 g(-1) for the cerebral blood flow. Small areas that exhibited a very high signal change upon labeling were indicative of regional variation in cerebral blood flow related to vascular anatomy. Copyright (C) 2004 John Wiley Sons. Ltd.

Localized magnetic resonance spectroscopy (MRS) yields sensitive metabolic markers to provide insight into the pathophysiology of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in vivo. Findings in full MELAS syndrome at 1H MRS of the brain typically include severely elevated lactate and reduced N-acetylaspartate, glutamate, myo-inositol, and total creatine concentrations in stroke-like lesions. Similar but less extreme alterations are also common in gray matter (GM) regions that appear normal at magnetic resonance imaging. Phosphorus spectroscopy of peripheral muscle permits investigation of the bioenergetic status. A decline of the phosphorylation potential indicates a low energy reserve at rest. Phosphocreatine resynthesis during post-exercise recovery is delayed pointing to reduced mitochondrial capacity. As MRS is inherently non-invasive, follow-up studies can be performed to assess treatment response quantitatively.

Continuous arterial spin labeling (CASL) using adiabatic inversion is a widely used approach for perfusion imaging. For the quantification of perfusion, a reliable determination of the labeling efficiency is required. A numerical method for predicting the labeling efficiency in CASL experiments under various experimental conditions, including spin relaxation, is demonstrated. The approach is especially useful in the case of labeling at the carotid artery with a surface coil, as consideration of the experimental or theoretical profile of the B 1 field is straightforward. Other effects that are also accounted for include deviations from a constant labeling gradient, and variations in the blood flow velocity due to the cardiac cycle. Assuming relevant experimental and physiological conditions, maximum inversion efficiencies of about 85% can be obtained. Magn Reson Med 51:1187–1193, 2004. © 2004 Wiley‐Liss, Inc.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.

Functional perfusion imaging (p-fMRI) was applied for the first time to a cognitive paradigm that produces activations in a number of brain regions. An adapted single-trial version of the color-word Stroop interference task was used as a paradigm. This experiment is known to produce robust activations in the lateral prefrontal, the fronto-median, and parietal cortices. Perfusion contrast was created by continuous arterial spin labeling (CASL) of the blood in the left common carotid artery, and was applied for all repetitions of the functional run in a quasi-continuous fashion, i.e., it was interrupted only during image acquisition. For imaging, a spin-echo (SE) echo planar imaging (EPI) sequence with a 64×36 acquisition matrix was used. A short echo time of TE=13 ms was employed in order to suppress blood oxygen level dependent (BOLD) signals. For comparison, BOLD contrast was detected using conventional gradient-echo (GE) or SE-EPI. Positive activations in BOLD imaging appear in p-fMRI as negative signal changes corresponding to an enhanced transport of inverted water spins into the region of interest (i.e., increased cerebral blood flow [CBF]). Negative BOLD responses (areas of deactivation) appear as positive signal changes in p-fMRI indicating areas with decreased CBF. p-fMRI was capable of reproducing most of the GE-BOLD-fMRI activations and deactivations as signal changes of opposite sign. The localization of the local maxima of p-fMRI agreed reasonably with SE-BOLD-fMRI and GE-BOLD-fMRI. Significant shifts between the covered areas of each contrast were also detected. In certain areas, p-fMRI yielded a low sensitivity compared to BOLD-fMRI. The quantification of CBF changes during cognitive task activation is demonstrated for several well-separated cortical areas. The observation of a decreased CBF during the Stroop task in the parietomedian cortex confirms previous PET results which showed decreases of CBF in well-separated cortical regions related to a decrease in neuronal activity.

Contrast generated by intermolecular double-quantum coherences (iDQC) is a novel approach to fMRI, which is qualitatively and quantitatively different from the standard blood oxygen level dependent (BOLD) contrast. Specifically, it was suggested that the sensitivity of iDQC to local susceptibility gradients can be adjusted on a mesoscopic scale (between 10µm and 1mm) externally by the experimenter. A drawback of iDQC experiments, however, is their inherently poor signal-to-noise ratio leading to substantial signal fluctuations in previous pilot studies. In the current work, parameters of modified CRAZED sequences were carefully optimized to achieve high signal stability in iDQC experiments at 3 T with the standard birdcage headcoil. Initial phantom experiments were utilized to verify that the detected signal was due to iDQC by recording its angular dependence. A four-step phase-cycling scheme was used to filter out specific multiple-quantum coherences. Contributions from unwanted coherence pathways at the center of the k-space were of the noise level. In in vivo experiments (series of 60 repetitions) in healthy volunteers a systematic variation of the repetition time (TR) yielded sufficient signal stability (as compared to ordinary EPI time series) if a relatively long TR 3 5s was used. A two-step phase cycling scheme was used in these experiments. A reason for the suboptimal signal stability at shorter TRs are contributions from additional stimulated echoes, which are not suppressed by the crusher gradients after image acquisition. fMRI studies were performed in 6 subjects with a simple visual paradigm (blocked design). In all subjects, both gradient-recalled echo (GRE) and spin-echo type iDQC sequences were recorded. Additional GRE or SE BOLD measurements were also performed. While no functional contrast was observed with SE-iDQC, functional maps were reproducibly obtained with GRE-iDQC (Fig. 1). These maps showed less activated pixels compared to routine BOLD experiments, however, the averaged functional signal change was >10% (GRE-iDQC) as compared to only 2% in the BOLD experiments. The optimized sequences provide a basis for future experimental investigations into the origin of the functional iDQC contrast.

Magnetic resonance imaging studies in patients with phenylketonuria (PKU) revealed white matter alterations that correlated to most recent blood phenylalanine (Phe) concentrations as well as to brain Phe concentrations measured by magnetic resonance spectroscopy. The clinical significance of these changes is unknown. Magnetic resonance imaging data thus have no impact on therapeutic recommendations for adolescents and adults with PKU. Kinetic investigations of patients by magnetic resonance spectroscopy showed differences in brain Phe concentrations despite similar blood Phe levels. These were influenced by interindividual variations of blood-brain barrier Phe transport constants and by variations of the individual brain Phe consumption rate. Blood-brain barrier Phe transport characteristics as well as brain Phe consumption rates thus seem to be causative factors for the individual outcome in PKU.

In vivo phosphorus magnetic resonance spectroscopy (MRS) was used to investigate markers of the cerebral energy status in two patients with glutaric aciduria type I (GA-I). Besides an increased concentration of phosphomonoesters in one patient, no other significant alterations from controls were found. This might indicate increased resynthesis of dendritic processes secondary to preceding metabolic crises. In contrast to previous cell-culture studies, no cerebral depletion of phosphocreatine (PCr) was observed. In conclusion, a severe global and permanent depletion of cerebral energy supplies must be ruled out. The benefit of a permanent creatine substitution to stabilize mitochondrial energy metabolism seems thus questionable. However, as MRS was performed during stable clinical conditions, the possibility of a PCr decrease during acute metabolic crises cannot be assessed.

Functional perfusion imaging with a separate labeling coil located above the common carotid artery was demonstrated in human volunteers at 3 T. A helmet resonator and a spin‐echo echo‐planar imaging (EPI) sequence were used for imaging, and a circular surface coil of 6 cm i.d. was employed for labeling. The subjects performed a finger‐tapping task. Signal differences between the condition of finger tapping and the resting state were between −0.5% and −1.1 % among the subjects. The imaging protocol included a long post‐label delay (PLD) to reduce transit time effects. Labeling was applied for all repetitions of the functional run to reduce the sampling interval. Magn Reson Med 49:791–795, 2003. © 2003 Wiley‐Liss, Inc.

The nuclear spin polarization of the noble gas isotopes 3He and 129Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments. Magn Reson Med 47:1029–1051, 2002. © 2002 Wiley‐Liss, Inc.

1 H magnetic resonance spectroscopy (MRS) of the brain and 31 P MRS and saturation transfer of resting skeletal muscle were used to investigate intracellular metabolites and fluxes through the creatine kinase (CK) reaction in a patient with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Acute cortical lesions were characterized by severely elevated lactate levels and reduced concentrations of N ‐acetylaspartyl compounds, glutamate, and myo‐inositol. Similar but less extreme alterations were also observed in gray matter regions that appeared normal on magnetic resonance images. Investigation of the gastrocnemius muscle at rest demonstrated a reduced phosphocreatine level, elevated concentrations of inorganic phosphate and free adenosine 5′‐diphosphate, and an abnormally low phosphorylation potential. Besides a moderately increased muscular phosphocreatine concentration, none of the metabolic disturbances detected on MRS improved with oral creatine supplementation. Forward and reverse fluxes through the CK reaction did not significantly change upon creatine treatment. Follow‐up MRS investigations may thus provide objective markers of treatment response in vivo without the hazards or inconvenience of biopsy. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002

Purpose: To prospectively determine the value of magnetic resonance imaging (MRI) with flow quantification in the portal vein for the follow-up of patients with transjugular intrahepatic portosystemic shunt (TIPS). Methods: Thirty-six patients with TIPS (23 m, 13 f) were evaluated with MR of the liver parenchyma and quantification of flow in the portal vein. MR examinations were correlated with Doppler sonography and conventional angiography including measurement of the portal pressure gradient (PPG). In cases of re-interventions (dilatation/stent application) additional examinations with MRI and Doppler sonography were performed. Results: MR flow measurements in the portal vein correlated with Doppler sonography (r = 0.69) whereas no correlation of both methods with the PPG was found. No threshold velocity in the portal vein could be determined to predict shunt stenosis. All shunt occlusions (n = 5) were diagnosed correctly by MRA. Thirty measurements before and after successful angiographic interventions revealed a significant increase in portal flow velocity and a significant decrease of the PPG. Magnetic resonance images enabled a reliable detection of procedural complications (parenchymal bleedings, n = 31; extra and subcaspular hematomas, n = 2 each) and newly occurring hepatocellular carcinomas (n = 2) in the follow-up period. Conclusion: Magnetic resonance imaging in the follow-up of TIPS enables a morphological assessment of the liver and an accurate velocity mapping, but is not suited to predict shunt dysfunction as a single method.

Different clinical outcomes in spite of comparable dietary controls are well known in patients with phenylketonuria. Currently, reasons for this phenomenon are unknown. Kinetic investigations in 15 patients with classic phenylketonuria were performed using in vivo nuclear magnetic resonance spectroscopy before and after an oral phenylalanine load (100 mg/kg body weight). Patients' brain phenylalanine concentrations were quite different in spite of similar blood phenylalanine levels. Interindividual variations of the apparent transport Michaelis constant, K(t,app), covered a range from 0.10 to 1.03 mmol/L. The ratio of the maximal transport velocity, Tmax, over the intracerebral consumption rate, Vmet, varied between 2.61 and 14.0. Both parameters as well as the preload brain phenylalanine levels correlated significantly with the degree of cerebral white matter abnormalities on magnetic resonance images. Correlations of K(t,app), Tmax/Vmet, and the preload brain phenylalanine levels with patients' intelligence scores approached significance. In conclusion, blood-brain barrier phenylalanine transport characteristics and the resultant brain phenylalanine levels seem to be causative factors for the individual clinical outcome in phenylketonuria. This observation may lead to individual dietary recommendations in the future.

Hyperpolarized He-3 spin-lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T-1 was dominated by interactions with oxygen and was used to measure the alveolar O-2 partial pressure. In animals ventilated with a mixture of 79% He-3 and 21% O-2, T-1 dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 +/- 11 mL min(-1) kg(-1) under normoxic conditions, and 9.0 +/- 2.0 mL min(-1) kg(-1) under hypoxic conditions. Cardiac output was estimated to be 400 +/- 160 mL min(-1) kg(-1). The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 +/- 0.3 mL and 10.7 +/- 1.1 mL. (C) 2001 Wiley-Liss, Inc.