Biomedical subjects

L L Wald

Publications and source records attributed to L L Wald.

At least 19 recordsLinked to original sources

PubMed2002

Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study.

RATIONALE: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. OBJECTIVES: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy ((31)P-MRS) before and after citicoline treatment. METHODS: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a (31)P-MRS scan at baseline and following 6 and 12 weeks of treatment. RESULTS: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters ( P=0.008), including an 11.6% increase in glycerophosphoethanolamine ( P=0.002) and a 5.1% increase in glycerophosphocholine ( P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. CONCLUSIONS: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.

Administration, Oral↗

PubMed2002

In vivo GABA+ measurement at 1.5T using a PRESS-localized double quantum filter.

A point-resolved spectroscopy (PRESS)-localized double quantum filter was implemented on a 1.5T clinical scanner for the estimation of gamma-amino butyric acid (GABA) concentrations in vivo. Several calibrations were found to be necessary for consistent results to be obtained. The apparent filter yield was approximately 38%; filter strength was sufficient to reduce the singlet metabolite peaks in vivo to below the level of the noise. Metabolite-nulled experiments were performed, which confirmed that significant overlap occurred between macromolecule signals and the GABA resonance at 3.1 ppm. Although the multiplet arm at 2.9 ppm was confirmed to be relatively free of contamination with macromolecules, some contribution from these and from peptides is likely to remain; therefore, the term GABA+ is used. GABA+ concentrations were estimated relative to creatine (Cr) at the same echo time (TE) in a group of controls, studied on two occasions. The GABA+ concentration in 35-ml regions of interest (ROIs) in the occipital lobe was found to be 1.4 +/- 0.2 mM, with scan-rescan repeatability of 38%.

Adult↗

PubMed2000

Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas.

BACKGROUND AND PURPOSE: Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role of rCBV in the determination of recurrent/residual disease in patients with treated gliomas. METHODS: Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions. RESULTS: In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively. CONCLUSION: This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.

Adult↗

PubMed1999

Lactate detection at 3T: compensating J coupling effects with BASING.

Detection of lactate by in vivo 1H magnetic resonance spectroscopy may provide a means of identifying regions of metabolic stress in brain and other human tissue, potentially identifying regional ischemia in stroke or necrosis in tumors. At higher field strengths (3 and 4 T), which have recently become available for whole-body human studies, the chemical shift difference between the doublet from the methyl protons and the quartet from the methine proton becomes comparable to the available radiofrequency (RF) pulse bandwidth. In this case "anomalous" J modulation occurs in PRESS and STEAM because the coupling partner of the observed resonance may or may not be refocused by the RF pulses depending on the position of the molecule within the voxel and the size of the chemical shift misregistration artifact. These anomalies lead to signal cancellation for echo times near odd multiples of 1/J (often used to highlight the inverted lactate doublet against nearby lipid peaks) in single voxel studies, and spatial variation of the doublet lineshape in chemical shift imaging studies, producing erroneous determination of relative lactate concentrations. While increasing the band-width of the RF pulses can reduce this effect by reducing the signal cancellation, some cancellation will always remain. A means of eliminating this effect using BASING/ MEGA (Mescher M et al. Solvent suppression using selective echo dephasing J Magn Reson A 1996;123:226-229; Star-Lack J et al. Improved water and lipid suppression for 3D PRESS CSI using RF band selective inversion with gradient dephasing (BASING). Magn Reson Med 1997;38: 311-321) water suppression pulses will be described, along with some of its limitations.

Humans↗

PubMed1999

NAA-weighted imaging of the human brain using a conventional readout gradient.

An imaging sequence incorporating two complementary forms of water suppression was used in conjunction with conventional readout and phase-encoding gradients to acquire images of N-acetylaspartate (NAA) in human brain. The sequence consisted of CHESS water suppression pulses followed by dual echo sequence to select the imaging volume and frequency-selective refocusing pulses with asymmetric crushers to further reduce the water signal. Spectra and conventional spectroscopic images acquired with the sequence demonstrated robust suppression of water and other resonances down field from the 2.0-ppm NAA resonance with 98% of the brain signal resulting from the 3.0-ppm to 2.0-ppm region. The technique was found to provide NAA maps with a large (256 x 128) imaging matrix and to allow a flexible tradeoff between signal to noise ratio (SNR), matrix size, data acquisition window length, and imaging time. Since spectral information is not directly obtained, the length of the data acquisition window is not determined by the spectral resolution needed to resolve the components of the brain spectrum, allowing a significantly shorter readout period. The shorter acquisition window could potentially facilitate the acquisition of multi-echo or multi-slice brain NAA maps.

Artifacts↗

PubMed1999

High spatial resolution 1H-MRSI and segmented MRI of cortical gray matter and subcortical white matter in three regions of the human brain.

High-resolution MR imaging and spectroscopic imaging were used to study differences in proton spectra between cortical gray matter and subcortical white matter in 23 normal volunteers using a 1.5 T scanner and surface coil receivers. A point-resolved spectroscopy (PRESS) volume with an 8 x 8 x 8 phase-encoding matrix was used to acquire over 1900 0.09-0.2 cc spectral voxels. The high-resolution (0.7 x 0.7 x 0.8 mm3 or 0.8 x 0.8 x 1 mm3) images were corrected for the surface coil reception profile and segmented into cerebrospinal fluid (CSF) and gray and white matter to correlate with the spectra. The data showed that N-acetyl aspartate (NAA) and creatine (Cr) were higher in the gray matter than in the white matter (NAA(g/w) = 1.4+/-0.36, Cr(g/w) = 1.4+/-0.41). Choline was significantly lower in the gray matter of the occipital lobe than in the white matter (0.73+/-0.19), but not significantly different in the other regions. NAA/Cho was found to be significantly higher in the occipital lobe than in the left frontal or vertex regions.

Adult↗

PubMed1999

Multislice perfusion and perfusion territory imaging in humans with separate label and image coils.

An arterial spin labeling technique using separate RF labeling and imaging coils was used to obtain multislice perfusion images of the human brain at 3 T. Continuous RF irradiation at a peak power of 0.3 W was applied to the carotid arteries to adiabatically invert spins. Labeling was achieved without producing magnetization transfer effects since the B1 field of the labeling coil did not extend into the imaging region or couple significant power into the imaging coil. Eliminating magnetization transfer allowed the acquisition of multislice perfusion images of arbitrary orientation. Combining surface coil labeling with a reduced RF duty cycle permitted significantly lower SAR than single coil approaches. The technique was also found to allow selective labeling of blood in either carotid, providing an assessment of the artery's perfusion territory. In normal subjects, these territories were well-defined and localized to the ipsilateral hemisphere.

Artifacts↗

PubMed1999

A phased array echoplanar imaging system for fMRI.

A fully parallel, simultaneous sampling phased array receiver system for a clinical echoplanar imaging system is described and evaluated for BOLD activation and relative cerebral blood volume (rCBV) experiments. A 4-coil array curved around the occipital lobe improved SNR by factors of 1.5 in the visual cortex and 3.1 in the visual association cortex relative to a 13-cm diameter surface coil, improving the statistical significance and coverage of visual activation maps. A 4-coil bilateral array increased SNR throughout the head relative to a quadrature head coil by up to a factor of 5 in much of the cortex, with proportional improvement in the SNR of rCBV maps.

Adult↗

PubMed1998

A localized double-quantum filter for the in vivo detection of brain glucose.

A double-quantum filter (DQF) sequence with PRESS localization was developed for in vivo detection of the glucose resonances in the 3.85-ppm region of the brain proton spectrum. The efficiency and spectral editing characteristics were studied in phantom and animal experiments. Approximately 45% detection efficiency was achieved at 4.7 T with TE = 68 ms. Since the efficiency of the DQF method is dependent on the relative phases of the RF pulses, a phase calibration procedure was used to correct for phase shifts induced by the spatial localization. In addition to detecting the 3.85-ppm glucose resonances with approximately 45% efficiency, the DQF sequence simultaneously detects 1.3-ppm lactate resonance with approximately 20% efficiency. The use of the DQF technique for simultaneously monitoring both the input and output of anaerobic glycolysis in the brain was demonstrated by detecting brain glucose and lactate in the same acquisition after iv injection of glucose followed by the induction of global ischemia.

Animals↗

PubMed1998

T1 effects in sequential dynamic susceptibility contrast experiments.

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence of T1 effects is now investigated with experiments in which T1 weighting is varied as well as with serial regional T1 measurements. Little evidence for significant residual T1 effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.

Adult↗

PubMed1997

Theory and application of array coils in MR spectroscopy.

The theory and application of array coils are reviewed in the context of phased array spectroscopy. The optimization of the signal-to-noise ratio from an array of coils is developed by considering the efficiency of a phased array transmit coil. This approach avoids the need to consider noise correlation, and should be useful in future considerations of transmit phased array coils for MR spectroscopy. Methods to characterize array coil performance, including fields and coupling are briefly summarized, along with methods to minimize the effects of mutual inductance. The signal-to-noise advantages of array coils over single coils are examined for both planar and cylindrical arrays. Numerical simulations of planar arrays of 2 x 2, 4 x 4 and 8 x 8 elements and constant overall dimension are compared to a single coil of the same size. The results demonstrate a significant improvement in sensitivity near the array coil. Although the benefits of the array decrease as a function of distance from the array, the array sensitivity never drops below that of a single coil with the same overall dimensions, or that of a single element of the array. Similar results are obtained for a sixteen element cylindrical array, which is compared to a standard quadrature birdcage coil using both computational methods and phantom measurements. The phased array techniques reviewed are demonstrated with proton spectroscopic images of the brain.

Brain↗

PubMed1997

In vivo detection of GABA in human brain using a localized double-quantum filter technique.

A proton MR spectral editing technique employing a spatially localized, double-quantum filter (DQF) was used to measure gamma-aminobutyric acid (GABA) in the human brain at 1.5 T. The double-quantum method provided robust, single-shot suppression of uncoupled resonances from choline, creatine, and NAA and allowed detection of the gamma CH2 GABA (3.0 ppm) resonance with 30% efficiency. Spatial localization of the GABA measurement was achieved by incorporating PRESS localization within the double-quantum excitation and detection sequence. A calibration technique was developed to adjust the relative phases of the RF pulses to maximize the in vivo double-quantum detection efficiency for an arbitrary voxel location. The sequence efficiency, degree of suppression of uncoupled reasonances, and characterization of the in vivo DQF technique was examined in phantom experiments and in a study of the occipital lobe of 10 normal subjects. The ratio of the 3.0-ppm GABA resonance to the 3.0-ppm creatine resonance was found to be 0.20 +/- 0.05 (SD).

Brain Chemistry↗

PubMed1997

Serial proton magnetic resonance spectroscopy imaging of glioblastoma multiforme after brachytherapy.

The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.

Aspartic Acid↗

PubMed1997

High-resolution surface-coil MR of cortical lesions in medically refractory epilepsy: a prospective study.

PURPOSE: To determine the role of surface-coil MR imaging in evaluating medically refractory neocortical partial epilepsy. METHODS: A prospective study of 25 patients with medically refractory neocortical partial epilepsy was performed. Head- and surface-coil images were reviewed by two neuroradiologists to determine the clarity with which cortical lesions were depicted. The ability of imaging, combined with surface electroencephalography (EEG), to locate the suspected epileptogenic zone was evaluated. RESULTS: Compared with head-coil studies, surface-coil studies showed four more lesions, caused the most probable diagnosis to be altered in five patients, and better defined the lesions in four patients. Of 11 patients with lobar EEG abnormalities, imaging showed focal cortical abnormalities within the same or adjacent lobe in five and multifocal abnormalities in two. Of six patients with EEG abnormalities restricted to two adjacent lobes, imaging showed focal cortical abnormalities in one of these lobes in five patients and multifocal abnormalities in one patient. Of eight patients with a nonfocal EEG, imaging showed focal cortical abnormalities in five and multifocal cortical abnormalities in one. In two of 13 patients, video/EEG telemetry improved seizure location whereas surface-coil imaging showed focal cortical lesions in six and provided relevant prognostic information in five. CONCLUSION: Compared with head-coil studies, surface-coil imaging of the cerebral cortex improved detection and differentiation of focal cortical lesions in 64% of patients. Video/EEG telemetry improved location in 15% of patients, and surface-coil imaging combined with EEG results provided improved location of the suspected epileptogenic zone or relevant prognostic information in 85%.

Adolescent↗

PubMed1996

A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses.

A proton magnetic resonance spectral editing technique is presented that uses PRESS excitation to achieve spatially localized measurements of brain gamma-aminobutyric acid (GABA). The homonuclear difference spectroscopy technique employs a frequency selective inversion pulse to suppress the creatine resonance at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances. The PRESS excitation achieves three dimensional spatial localization in a single acquisition making it less sensitive to patient motion than multiple acquisition techniques. The performance and utility of this technique were evaluated by phantom experiments and by in vivo measurements of brain GABA concentration in 10 normal subjects.

Brain↗

PubMed1995

Phased array detectors and an automated intensity-correction algorithm for high-resolution MR imaging of the human brain.

Two- and four-coil phased array detectors were developed to increase the sensitivity and resolution of MR imaging of the human brain cortex, especially for detecting cortical dysplasias in pediatric epilepsy patients. An automated intensity correction algorithm based on an edge-completed, low-pass filtered image was used to correct the image intensity for the inhomogenous reception profile of the coils. Seven phased array coils were constructed and tested. The sensitivity of these coils was up to 600% higher at the surface of the cortex than that achieved with a conventional head coil and up to 30% greater at the center of the head. The sensitivity obtained was comparable with that of a conventional small surface coil, but extended over the larger dimensions of the array and previously inaccessible areas such as the top of the head. The advantages of the improved sensitivity are demonstrated with high resolution images of the brain.

Adult↗

PubMed1995

Proton spectroscopic imaging of the human brain using phased array detectors.

Two and four-coil phased array detectors have been developed to increase the sensitivity of proton spectroscopic imaging of the human brain. These include a quadrature figure-8 coil for the study of the vertex, several arrays of 2-4 small overlapping (6-8 cm diameter) circular coils and a combination figure-8 coil plus circular coil. These were constructed in our laboratory and tested to assess their utility for brain spectroscopy. Methods for optimally combining the data from the independent receivers based on the analytical coil maps or measured signal to noise ratios (SNRs) of the data were investigated. High spatial resolution (0.2-0.4 cm3 voxel size) two- or three-dimensional chemical shift images of normal brain were obtained in 17-minute acquisitions. These spatial resolutions are comparable to those previously obtained with conventional small surface coils, but the specialized detectors allow this sensitivity to be achieved for a larger region or for previously inaccessible areas such as the top of the head. The coverage and SNR increases demonstrated are similar to those obtained in magnetic resonance phased array imaging.

Brain↗

PubMedDate not supplied

High resolution T2-weighted imaging of the human brain using surface coils and an analytical reception profile correction.

High spatial resolution T2-weighted MR images of the human brain were obtained at 1.5 T. An optimized fast spin-echo (FSE) sequence and 1.5 g/cm gradients were used to obtain T2-weighted images in 4 to 9 minutes with an in-plane resolution of .27 mm and slice thicknesses from 1.5 to 3 mm. Phased arrays of surface coils were used as receivers, providing increased sensitivity but image intensities dependent on the reception profile of the coils. This image nonuniformity was removed by analyzing the data with a theoretical intensity correction algorithm developed in this laboratory. The FSE sequences, the specialized phased arrays of surface coils, and the intensity correction algorithm allowed improved visualization of nerves within the inner auditory canals and surface anatomy of the cerebral cortex. It is expected that this technique will be useful for clinical applications that require high resolution imaging of small, superficial structures of the brain.

Algorithms↗