Gd-DTPA bolus tracking in the myocardium using T1 fast acquisition relaxation mapping (T1 FARM).

MRI methods currently used for bolus tracking in the myocardium, such as saturation recovery turbo-fast low-angle shot (FLASH) (srTFL), are limited by signal intensity (SI) saturation at high contrast agent (CA) concentrations. By using T1 fast acquisition relaxation mapping (T1 FARM), a Gd-DTPA bolus (0.075 vs. 0.025 mmol/kg) may be injected without causing saturation. This study tested the feasibility of in vivo T1 FARM bolus tracking under rest/stress conditions in seven beagles with multiple permanently occluded branches of the left anterior descending (LAD) coronary artery. Although it underestimated the myocardial perfusion reserve (MPR) measured ex vivo using radioactive microspheres (mean +/- SEM; 3.60 +/- 0.26), the MPR determined upon application of the modified Kety model (1.86 +/- 0.10) enabled distinction between normal and infarcted tissue. The partition coefficient (lambda) estimated at rest and stress using the modified Kety model underestimated ex vivo radioactive measurements in infarcted tissue (0.25 +/- 0.01 vs. 0.26 +/- 0.01 vs. 0.79 +/- 0.08 ml/g, P < 0.0001) yet was accurate in normal tissue (0.28 +/- 0.01 vs. 0.30 +/- 0.01 vs. 0.33 +/- 0.01 ml/g, P = NS). Thus, although unsuitable for myocardial viability assessment, T1 FARM bolus tracking shows potential for assessment of myocardial perfusion.

Magnetic field exposure and behavioral monitoring system.

To maximize the availability and usefulness of a small magnetic field exposure laboratory, we designed a magnetic field exposure system that has been used to test human subjects, caged or confined animals, and cell cultures. The magnetic field exposure system consists of three orthogonal pairs of coils 2 m square x 1 m separation, 1.751 m x 0.875 m separation, and 1.5 m x 0.75 m separation. Each coil consisted of ten turns of insulated 8 gauge stranded copper conductor. Each of the pairs were driven by a constant-current amplifier via digital to analog (D/A) converter. A 9 pole zero-gain active Bessel low-pass filter (1 kHz corner frequency) before the amplifier input attenuated the expected high frequencies generated by the D/A conversion. The magnetic field was monitored with a 3D fluxgate magnetometer (0-3 kHz, +/- 1 mT) through an analog to digital converter. Behavioral monitoring utilized two monochrome video cameras (viewing the coil center vertically and horizontally), both of which could be video recorded and real-time digitally Moving Picture Experts Group (MPEG) encoded to CD-ROM. Human postural sway (standing balance) was monitored with a 3D forceplate mounted on the floor, connected to an analog to digital converter. Lighting was provided by 12 offset overhead dimmable fluorescent track lights and monitored using a digitally connected spectroradiometer. The dc resistance, inductance of each coil pair connected in series were 1.5 m coil (0.27 Omega, 1.2 mH), 1.75 m coil (0.32 Omega, 1.4 mH), and 2 m coil (0.38 Omega, 1.6 mH). The frequency response of the 1.5 m coil set was 500 Hz at +/- 463 microT, 1 kHz at +/- 232 microT, 150 micros rise time from -200 microT(pk) to + 200 microT(pk) (square wave) and is limited by the maximum voltage ( +/- 146 V) of the amplifier (Bessel filter bypassed).

A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls exposed to a pulsed (200 microT) magnetic field: effects on normal standing balance.

Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF's on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.

Human subjects exposed to a specific pulsed (200 microT) magnetic field: effects on normal standing balance.

Static and time-varying magnetic fields have been shown to alter animal and human behaviors, such as directional orientation, learning, pain perception (nociception or analgesia) and anxiety-related behaviors. Human volunteers (12 male, 12 female, 18-34 years old) stood on a force plate while within three square magnetic field coil pairs (2, 1.75 and 1.5 m) arranged orthogonal with the uniform magnetic field volume centered at head level. Analysis of the data shows a significant improvement of normal standing balance or center of pressure, with eyes open or eyes closed, by a specific pulsed 200 microT(pk) magnetic field (PEMF). There was no significance found in control condition testing, such as sham-sham exposure of subjects or sham/PEMF exposure of a 60 kg saline phantom. There were no significant effects of gender or age.

Spectroscopic lineshape correction by QUECC: combined QUALITY deconvolution and eddy current correction.

Lineshape distortion due to residual eddy currents and magnetic field inhomogeneities are often present in short echo time (1)H spectroscopic data. Lineshape correction methods such as QUALITY deconvolution and eddy current correction (ECC), which use a separate reference spectrum for lineshape correction, have shortcomings when unsuppressed water is chosen as the reference. This paper outlines a method of integrating both techniques to overcome these limitations while still using unsuppressed water as the reference signal. This hybrid lineshape correction technique (QUECC) is demonstrated in vivo using stimulated echo acquisition mode (STEAM) localized 4.0 Tesla data. Metabolite quantification precision increased by an average of 7%-46% compared to QUALITY deconvolution (depending on filtering) and by an average of 6% compared to ECC.

Comparison of the quantification precision of human short echo time (1)H spectroscopy at 1.5 and 4.0 Tesla.

Precise quantification of human in vivo short echo time (1)H spectra remains problematic at clinical field strengths due to broad peak linewidths and low signal-to-noise ratio (SNR). In this study, multiple STEAM spectra (TE = 20 ms, volume = 8 cm(3)) were acquired in a single individual at 1.5 T and 4 T to compare quantification precision. Test-retest STEAM spectra (volume = 1.5 cm(3)) were also acquired from the anterior cingulate and thalamus of 10 individuals at 4.0 T. Metabolite levels were quantified using automated software that incorporated field strength-specific prior knowledge. With the distinct methods of data acquisition, processing, and fitting used in this study, peak height SNR increased approximately 80% while peak linewidth increased by approximately 50% in the 8 cm(3) volumes at 4.0 T compared to 1.5 T, resulting in an average increase in quantification precision of 39%. Metabolite levels from test-retest data (1.5 cm(3) voxels at 4.0 T) were quantified with similar inter- and intraindividual variability. Magn Reson Med 44:185-192, 2000. Published 2000 Wiley-Liss, Inc.

T(1) fast acquisition relaxation mapping (T(1)-FARM): optimized data acquisition.

A theoretical procedure for estimating the precision of the T(1) Fast Acquisition Relaxation Mapping sequence as a function of a number of acquisition parameters has been validated by both simulations and experimental results. These results have clarified the selection of sequence parameters to give optimal accuracy and precision in the R(1)* measurements. There is excellent agreement between theory, simulation, and experiment except for flip angles greater than 9 degrees, at which point slice profile imperfections significantly degrade the precision of the technique. The experimental results indicate that over a range of T(1)s that would be seen in a bolus tracking experiment (25-1200 ms), T(1) Fast Acquisition Relaxation Mapping can be used to obtain 64 x 128 R(1)* maps at a rate of 1 map/s, with a precision of 10% or better.

Factors affecting the quantification of short echo in-vivo 1H MR spectra: prior knowledge, peak elimination, and filtering.

Short echo 1H in-vivo brain MR spectra are difficult to quantify for several reasons: low signal to noise ratio, the severe overlap of spectral lines, the presence of macromolecule resonances beneath the resonances of interest, and the effect of resonances adjacent to the spectral region of interest (SRI). This paper outlines several different quantification strategies and the effect of each on the precision of in-vivo metabolite measurements. In-vivo spectra were quantified with no operator interaction using a template of prior knowledge determined by mathematically modeling separate in-vitro metabolite spectra. Metabolite level estimates and associated precision were compared before and after the inclusion of macromolecule resonances as part of the prior knowledge, and following two different methods of handling resonances adjacent to the SRI. The effects of rectangular and exponential filters were also investigated. All methods were tested using repeated in-vivo spectra from one individual acquired at 1.5 T using stimulated echo acquisition mode (STEAM, TE = 20 ms) localization. The results showed that the inclusion of macromolecules in the prior knowledge was necessary to obtain metabolite levels consistent with the literature, while the fitting of resonances adjacent to the SRI concurrent with modeled metabolites optimized the precision of metabolite estimates. Metabolite levels and precision were also affected by rectangular and exponential filtering, suggesting caution must be taken when such filters are used.

A short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients.

BACKGROUND: Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter. METHODS: Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes. RESULTS: No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects. CONCLUSIONS: Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter.

Improved contrast agent bolus tracking using T1 FARM.

Current MRI bolus tracking techniques, such as saturation recovery Turbo-FLASH (srTFL), suffer from signal saturation at high contrast concentrations. In this study T1 Fast Acquisition Relaxation Mapping (T1 FARM) was compared to srTFL. In phantoms, T1 FARM maps were linear with [Gd-DTPA] up to 7.0 mmol/L while srTFL images saturated above 2.0 mmol/L. In the canine left ventricle, blood concentration curves determined from T1 FARM saturated with bolus injections exceeding 0.075 mmol/kg, while srTFL curves saturated above 0.025 mmol/kg of Gd-DTPA. Also, T1 FARM improved contrast-to-noise ratio in tissue concentration curves since higher contrast concentrations could be measured without saturating.

A 1H-decoupled 31P chemical shift imaging study of medicated schizophrenic patients and healthy controls.

BACKGROUND: Current 31P spectroscopy research in schizophrenia has examined phospholipid metabolism by measuring the sum of phosphomonoesters and the sum of phosphodiester-containing molecules. Proton decoupling was implemented to measure the individual phosphomonoester and phosphodiester components. This is the first study employing this technique to examine schizophrenic patients. METHODS: Multivoxel two-dimensional chemical shift in vivo phosphorous-31 magnetic resonance spectroscopy with proton decoupling was used to examine a 50-cm3 volume in prefrontal, motor, and parieto-occipital regions in the brain. Eleven chronic medicated schizophrenic patients were compared to 11 healthy controls of comparable gender, education, parental education, and handedness. RESULTS: A significant increase in the mobile phospholipid peak area and its full width at half maximum was observed in the medicated schizophrenic patients compared to the healthy controls in the prefrontal region. Inorganic orthophosphate and phosphocholine were lower in the schizophrenic group in the prefrontal region. CONCLUSIONS: The increased sum of phosphodiester [mobile phospholipid + glycerol-3-phosphoethanolamine (GPEth) + glycerol-3-phosphocholine (GPCh)] in schizophrenic patients, measured in earlier studies, arises from the phospholipid peak (MP) and not the more mobile phosphodiesters (GPEth, GPCh) as was originally suspected. A decrease in the phosphocholine component of the phosphomonoesters was also observed in the schizophrenic patients. These findings are consistent with an abnormality in membrane metabolism in the prefrontal region in schizophrenics.

Quantifying 1H decoupled in vivo 31P brain spectra.

Our objective was to develop a precise method for quantification of in vivo proton decoupled 31P spectra from the human brain. This objective required that an appropriate spectral model be created and that the quantification was performed using a non-subjective fitting technique. The precision of the quantification was assessed using Cramer-Rao standard deviations and compared using two different spectral models: one containing a pair of peaks representing 2,3-diphosphoglycerate, the other excluding this metabolite. The data was quantified using a Marquardt-Levenberg (ML) algorithm incorporating prior knowledge with a Hankel singular value decomposition (HSVD) performed initially to provide parameter estimates for the ML algorithm. Quantification was performed on two different in vivo 2-D CSI 31P data sets: the first examined 11 normal controls, the second examined a single individual six times. Spectra from a region in the parieto-occipital cortex were analyzed. The Cramer-Rao standard deviations were significantly lower for some metabolites with 2,3-diphosphoglycerate in the model: in the repeat study mobile phospholipids (p = 0.045) and phosphocholine (p = 0.034), and in the 11 controls mobile phospholipids (p = 0.003) and Pi (p = 0.002).

Fast acquisition of quantitative T2 maps.

A rapid new technique called T2 fast acquisition relaxation mapping (T2 FARM) was developed to allow T2 maps to be reconstructed directly from k-space data acquired in 3 sec. A single acquisition measured two sets of k-space data, the first with T1 and T2 weighting independent of phase encode position, and the second with T2 weighting varying with phase encode position. These data were processed using an iterative least squares algorithm to produce a quantitative T2 map from the k-space data. T2 values of phantoms and an egg were determined from T2 FARM maps and spectroscopic Carr-Purcell-Meiboom-Gill (CPMG) measurements, demonstrating the validity of the new technique.

A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects.

OBJECTIVE: It is likely that the corpus striatum is involved in obsessive-compulsive disorder (OCD). Prior studies have inconsistently found alterations in caudate volumes in patients with OCD. This study was undertaken in the hope that N-acetylaspartate and volumetric measures together would elucidate the presence and nature of corpus striatum volumetric abnormalities in OCD. METHOD: Thirteen patients meeting the DSM-IV criteria for OCD, who had been medication free for a minimum of 6 weeks, and 13 psychiatrically normal matched comparison subjects participated in the study. Short echo 1H magnetic resonance spectroscopy (1H-MRS) was used to measure levels of N-acetylaspartate and several other cerebral metabolites from a 4.5-cm3 volume in the left corpus striatum of all 26 subjects. Metabolite levels were estimated by fitting the time domain spectroscopy data with a noninteractive computer program. Volumes of the left and right head of the caudate nucleus in each subject were determined by semiautomatic segmentation of the volumetric images. RESULTS: N-Acetylaspartate levels from the left corpus striatum were significantly lower in the patients with OCD than in the comparison subjects. There were no differences in either left or right caudate volume between the two groups. CONCLUSIONS: Despite the lack of differences in caudate volumes between the OCD patients and the comparison subjects, the lower level of N-acetylaspartate in the left corpus striatum of the patients suggests reduced neuronal density in this region. Inconsistent volumetric findings among prior studies may reflect a poorer sensitivity of magnetic resonance imaging morphometry for detecting neuronal loss compared with 1H-MRS measurement of N-acetylaspartate.

Myocardial infarction in a canine model monitored by two-dimensional 31P chemical shift spectroscopic imaging.

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12-ml voxels were noninvasively tracked using 31P two-dimensional chemical shift imaging. Gadolinium enhanced 1H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7+/-8.8% (mean+/-SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base-line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3-0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.

Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy.

BACKGROUND: Positron emission tomographic and postmortem studies comparing schizophrenic patients with healthy control subjects have found medial prefrontal cortical and anterior cingulate abnormalities that suggest dysfunction in glutamatergic neurons. The glutamate used for nerve signal transduction is predominantly derived from glutamine. After signal transduction, glutamate released into the synapse is converted to glutamine in glial cells, transported back to the presynaptic neuron, and reconverted to glutamate for reuse. In this study, levels of glutamate and glutamine were examined by means of in vivo proton (1H) magnetic resonance spectroscopy. METHODS: Localized in vivo 1H spectra were acquired from a 4.5-cm3 volume in the left medial prefrontal cortex encompassing portions of Brodmann areas 24, 32, and 9 in 10 never-treated schizophrenic subjects and 10 healthy controls of comparable age, sex, handedness, education, and parental education. From each spectrum, metabolite levels were estimated for glutamate and glutamine, as well as 10 other metabolites and 3 macromolecules, by means of a noninteractive computer program that combined modeled in vitro spectra of every metabolite to reconstruct each in vivo spectrum. RESULTS: A significant increase in glutamine level was found in the medial prefrontal cortex of the schizophrenic patients compared with controls. N-acetylaspartate and other measured metabolites and macromolecules were not significantly changed in schizophrenics. CONCLUSION: Increased glutamine levels in the medial prefrontal region most likely reflect decreased glutamatergic activity in this region in never-treated schizophrenic patients compared with healthy controls.

Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.

The purpose of this study was to examine the relationship between phosphorus magnetic resonance spectroscopy (31P MRS) parameters and left prefrontal volumes in both patients with schizophrenia and healthy subjects. 31P MRS parameters and magnetic resonance imaging (MRI) volumetric data were collected in the left prefrontal region in 10 patients with schizophrenia and 10 healthy subjects of comparable age, handedness, sex, educational level, and parental educational level. No correlations were found between any MRS parameter and grey matter volumes in the combined subjects. Phosphomonoester (PME) and grey matter volumes, however, were both correlated negatively with age. PMEs were found to be decreased, and calculated intracellular magnesium ([Mg2+]intra) was found to be increased in the patients with schizophrenia compared with healthy subjects after adjusting for left prefrontal grey and white matter, total brain volume, and age. These findings suggest that cortical grey and white manner volumes are not directly related to PME and [Mg2+]intra abnormalities in schizophrenia patients.

An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients.

The level of the 1H metabolites in the left dorsolateral prefrontal region of schizophrenia patients at different stages of illness were measured in vivo using a short echo time spectroscopy technique. During both the early onset and chronic stages, normal N-acetylaspartate levels were observed, which suggests that these patients had no significant neuronal cell damage and/or loss. The in vivo measurements of glutamate in the first-episode, drugnaive patients failed to provide convincing evidence for the involvement of the glutamatergic system in the dorsolateral prefrontal region. Significant differences in the glutamine levels were observed in the acutely medicated and chronic patients; however, the interpretation of these differences requires further study.

The use of a priori knowledge to quantify short echo in vivo 1H MR spectra.

In vivo 1H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8-cm3 volume of interest (VOI) and a 4-cm3 VOI positioned within the 8-cm3 VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho(t)) between spectra from the 8- and 4-cm3 VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from 1H images). Correcting for the T1 and T2 relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho(t), Glu, and glutamine were consistent with previous in vivo and in vitro reports.