Theory of MRI in the presence of zero to low magnetic fields and tensor imaging field gradients.

Today, all commonly practiced magnetic resonance imaging (MRI) reconstruction methods assume that the magnetic field created by the gradient coils is everywhere truncated by a dominant static uniform magnetic field. However, with the advent of SQUID detected MRI at microtesla fields, the opposite limit attracts attention, i.e., image formation in the unperturbed tensor field of the gradient coils. Here, we show by numerical simulations that, in principle, it is possible to reconstruct the image of an object in the absence of a uniform static field, working with the same gradient field setup as used in conventional MRI. Our calculations show that this approach could increase the image resolution limit attainable at low fields with a minimal incorporation of additional hardware and pulse sequences.

NMR detection using laser-polarized xenon as a dipolar sensor.

Hyperpolarized (129)Xe can be used as a sensor to indirectly detect NMR spectra of heteronuclei that are neither covalently bound nor necessarily in direct contact with the Xe atoms, but coupled through long-range intermolecular dipole-dipole interactions. To reintroduce long-range dipolar couplings the sample symmetry has to be broken. This can be done either by using an asymmetric sample arrangement, or by breaking the symmetry of the spin magnetization with field gradient pulses. Experiments are performed where only a small fraction of the available (129)Xe magnetization is used for each point, so that a single batch of xenon suffices for the point-by-point acquisition of a heteronuclear NMR spectrum. Examples with (1)H as the analyte nucleus show that these methods have the potential to obtain spectra with a resolution that is high enough to determine homonuclear J couplings. The applicability of this technique with remote detection is discussed.

Hyperpolarized xenon nuclear spins detected by optical atomic magnetometry.

We report the use of an atomic magnetometer based on nonlinear magneto-optical rotation with frequency-modulated light to detect nuclear magnetization of xenon gas. The magnetization of a spin-exchange-polarized xenon sample (1.7 c m(3) at a pressure of 5 bars, natural isotopic abundance, polarization 1% ), prepared remotely to the detection apparatus, is measured with an atomic sensor. An average magnetic field of approximately 10 nG induced by the xenon sample on the 10 cm diameter atomic sensor is detected with signal-to-noise ratio approximately 10 , limited by residual noise in the magnetic environment. The possibility of using modern atomic magnetometers as detectors of nuclear magnetic resonance and in magnetic resonance imaging is discussed. Atomic magnetometers appear to be ideally suited for emerging low-field and remote-detection magnetic resonance applications.

Proton magnetic resonance spectroscopy characteristics of a focal cortical dysgenesis during status epilepticus and in the interictal state.

We report the magnetic resonance imaging and proton magnetic resonance spectroscopic findings ((1)HMRS) in a patient with a focal cortical dysgenesis in the right superior frontal gyrus during intermittent frontal status epilepticus (IFSE) with simple partial seizures, and after she had become seizure free. During the status epilepticus, demonstrated by simultaneous behavioural and electroencephalographic telemetric long-term monitoring with scalp electrodes and ictal SPECT, we performed a single voxel spectroscopy of the dysgenic cortex. The(1)HMRS was repeated after 20 days when the patient's seizures were controlled. The N-acetyl-aspartate concentration in the focal dysgenic cortex was decreased in the interictal state but more during IFSE. The creatine/phosphocreatine concentration was normal in both instances. There was a clear lactate signal during IFSE, which was no longer visible in the interictal state. To our knowledge this is the first report of a(1)HMRS study of a focal cortical dysgenesis during an intermittent status epilepticus. We interpret the observed changes as signs of histopathological changes inherent to a cortical malformation and of an impaired energy metabolism due to the partial status epilepticus.

Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS.

OBJECTIVE: Glutathione in its reduced form (GSH) is the most important free radical scavenging compound in the mammalian nervous system that prevents membrane lipid peroxidation. It is suspected that epileptic seizures are accompanied by a massive production of reactive oxygen species, i.e., oxidative stress. METHODS: Using an (1)H MRS technique developed at the authors' site, the authors measured glutathione levels in a volume of interest (VOI) of 25 x 25 x 25 mm placed in structurally normal-appearing tissue in the parietooccipital region of each hemispheres in patients with and without active epilepsy, and in a age-matched control group. RESULTS: The GSH/water ratio in patients with epilepsy was significantly reduced in the parietooccipital region of both hemispheres (1.6 +/- 1.0 x 10(-5)) compared to the GSH/water ratio in healthy controls (2.4 +/- 1.1 x 10(-5)). There was no significant difference between the hemisphere with epileptogenic focus and the hemisphere without epileptogenic focus. The GSH/water ratios of the patients without active epilepsy were not different from the GSH/water ratios of patients with active epilepsy. CONCLUSION: The authors found evidence for a widespread impairment of the glutathione system in patients with epilepsy independent from seizure activity.

Improved selectivity of double quantum coherence filtering for the detection of glutathione in the human brain in vivo.

An improved double quantum coherence (DQC) filter for the selective in vivo detection of glutathione (GSH) in the human brain at 1.5 Tesla is presented. The goal was to minimize contamination of the DQC-filtered GSH signal at 2.9 ppm with contributions arising from GABA. The modification consists of tailoring the frequency response of the read pulse, which converts DQC into anti-phase single quantum coherence in such a way that the GABA beta and gamma resonances at 3.0 and 1.9 ppm, respectively, remain unaffected. An implementation incorporating a Dante pulse train is used for in vitro tests as well as for in vivo applications. Magn Reson Med 45:708-710, 2001.

Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.

Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.

Single-quantum coherence filter for strongly coupled spin systems for localized (1)H NMR spectroscopy.

A pulse sequence for localized in vivo (1)H NMR spectroscopy is presented, which selectively filters single-quantum coherence built up by strongly coupled spin systems. Uncoupled and weakly coupled spin systems do not contribute to the signal output. Analytical calculations using a product operator description of the strongly coupled AB spin system as well as in vitro tests demonstrate that the proposed filter produces a signal output for a strongly coupled AB spin system, whereas the resonances of a weakly coupled AX spin system and of uncoupled spins are widely suppressed. As a potential application, the detection of the strongly coupled AA'BB' spin system of taurine at 1.5 T is discussed.

Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering.

The feasibility of selective in vivo detection of glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH) in the human brain by means of (1)H magnetic resonance spectroscopy (MRS) at 1.5 T is demonstrated. A double quantum coherence (DQC) filtering sequence was used in combination with PRESS volume selection. The strongly coupled cysteinyl CH(2) compound of GSH was found to be the most suitable target for spectral editing. Analytical calculations employing a product operator description of the cysteinyl ABX three-spin system were made in order to optimize the inherent yield of the sequence. A pulse phase calibration procedure, which precedes the spectrum acquisition, secures maximal signal yield independently of the spatial localization of the volume of interest and thus comparability between individual examinations. In vitro tests show that the DQC filtering method provides good discrimination between the GSH signal at 2.9 ppm and the interfering resonances of creatine, gamma-aminobutyric acid (GABA) and aspartate. In measurements in the frontal lobe of 12 healthy volunteers a mean ratio of GSH signal to tissue water signal of 5.7 +/- 2.3 x 10(-5) was found, corresponding to a mean GSH tissue concentration of 2-5 mmol/L. The proposed technique allows for the detection of a biologically highly relevant metabolite at moderate field strength. Magn Reson Med 42:283-289, 1999.

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo.

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.

Quantitative 1H MRS of the human brain in vivo based on the stimulation phantom calibration strategy.

Normal metabolite concentrations were determined in five different brain regions of healthy adult volunteers using proton magnetic resonance spectroscopy (1H MRS) in vivo. The absolute in vivo concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cre), and choline containing compounds (Cho) were quantified from measurements obtained with a head-shaped simulation phantom. Scanner performance and calibration accuracy were assessed by phantom experiments. Localized spectra were acquired on clinical 1.5 T systems using the PRESS localization sequence with frequency selective water suppression. Comparison of the results obtained from phantom experiments and human brain in vivo strongly suggests that reproducibility in vivo mainly depends on the topologic metabolite heterogeneity of brain tissue in combination with relative volume dislocalization.

Detection of hidden metabolites by localized proton magnetic resonance spectroscopy in vivo.

Magnetic resonance spectroscopy (MRS) allows the assessment of chemical substances in living tissue and the detection of biochemical changes associated with certain diseases. In vivo MRS, however, is usually limited in sensitivity and spectral resolution. Many resonance lines originating from metabolites of interest are overlapped by signals of other metabolites and are therefore not visible in conventional MR spectra. In order to overcome this limitation, three localized methods, a technique making use of a spectral difference, a multiple quantum filter technique, and a two-dimensional J-resolved technique, were evaluated theoretically and experimentally for the detection of gamma-aminobutyric acid (GABA) both in vitro and in vivo. All three methods are able to produce the desired results at high metabolite concentrations in vitro. For in vivo measurements the spectral difference method proofed to be most appropriate due to its relatively high sensitivity and its short acquisition time.