PubMed Health⌕ Search

Biomedical subjects

David N Guilfoyle

Publications and source records attributed to David N Guilfoyle.

10 recordsLinked to original sources
PubMed2006

Using proton magnetic resonance imaging and spectroscopy to understand brain "activation".

Upon stimulation, areas of the brain associated with specific cognitive processing tasks may undergo observable physiological changes, and measures of such changes have been used to create brain maps for visualization of stimulated areas in task-related brain "activation" studies. These perturbations usually continue throughout the period of the stimulating event, and then subside when the event is terminated. In this communication, we consider the nature and meaning of these task-related brain activations. Since stimulation usually results in an increase in the frequency of neuron depolarizations or "spikes", an energy expensive activity that requires ATP for restoration of ionic gradients, additional energy supplies must be rapidly deployed to the stimulated areas or rates of re-polarization could be decreased, and refractory periods between spikes increased. As a result, maximum spiking rates may be decreased and some frequency-encoded information lost. The energy available to brain cells to re-synthesize ATP from ADP is a function of levels of glucose and oxygen in blood, and their availability to stimulated neurons is a function of the rate at which focal blood supplies can be increased (hyperemia). In this review we explore how neurons transmit meaningful encoded information; how the integrity of that information is dependent on a continuous supply of energy, and how proton magnetic imaging and spectroscopy may aid in understanding the process. Finally, evidence is presented that the neuropeptide, N-acetylaspartylglutamate, is a neuronal astrocyte-vascular feedback signal that regulates activation induced focal hyperemic responses.

Animals↗
PubMed2006

Interleaved snapshot echo planar imaging of mouse brain at 7.0 T.

Single-shot echo planar imaging (EPI) of a mouse brain at high field is very challenging. Large susceptibility-induced gradients affect much of the brain volume, causing severe image deformations and signal loss. Segmented EPI and other conventional multi-shot approaches alleviate these problems but suffer from lower temporal resolution and motion artifacts. We demonstrate that interleaved snapshot EPI represents a simple and robust alternative approach and one that is particularly suitable for high-field T2*-weighted functional imaging of a mouse brain. Similarly to segmented multi-shot techniques, it significantly reduces the susceptibility-related artifacts. At the same time, it preserves the high temporal resolution and the snapshot capability of a conventional EPI by acquiring entire image within a single TR period. We discuss implementation details of the interleaved snapshot EPI sequence and the trade-offs involved between the imaging efficiency, the number of interleaved excitation-acquisition blocks and the artifact reduction. To document the sequence utility, murine brain in vivo imaging with the interleaved snapshot EPI method was compared with a conventional EPI. We found that at least five interleaved blocks were necessary to restore the signal in most cortical areas. We also show that a standard global shimming procedure provides sufficient homogeneity for multi-slice interleaved snapshot EPI acquisition. In contrast, the conventional EPI of comparable image quality would be limited to a single slice with highly optimized local shim. Finally, an in vitro comparison with turbo FLASH acquisition shows the interleaved snapshot EPI to have superior time resolution and signal-to-noise ratio.

Animals↗
PubMed2005

2-PMPA, a NAAG peptidase inhibitor, attenuates magnetic resonance BOLD signals in brain of anesthetized mice: evidence of a link between neuron NAAG release and hyperemia.

N-acetylaspartylglutamate (NAAG), a dipeptide derivative of N-acetylaspartate (NAA) and glutamate (Glu), is present in neurons. Upon neurostimulation, NAAG is exported to astrocytes where it activates a specific metabotropic Glu surface receptor (mGluR3), and is then hydrolyzed by an astrocyte-specific enzyme, NAAG peptidase, liberating Glu, which can then be taken up by the astrocyte. NAAG is a selective mGluR3 agonist, one of several mGluRs that, when activated, triggers Ca2+ waves that spread to astrocytic endfeet in contact with the vascular system, where a secondary release of vasoactive agents induces a focal hyperemic response providing increased oxygen and nutrient availability to the stimulated neurons. Changes in blood oxygen levels can be assessed in vivo using a blood oxygenation level-dependent (BOLD) magnetic resonance imaging technique that reflects a paramagnetic effect of deoxyhemoglobin. In this study we used the competitive NAAG peptidase inhibitor 2-(phosphonomethyl) pentanedioic acid (2-PMPA) as a probe to interrupt the NAAG-mGluR3- Glu-astrocyte Ca2+ activation sequence. Using this probe, we investigated the relationship between release of the endogenous neuropeptide NAAG and brain blood oxygenation levels, as measured by changes in BOLD signals. In an anesthetized mouse, using an overtly nontoxic dose of 2-PMPA of 250 mg/kg i.p., there was an initial global BOLD signal increase of about 3% above control, lasting about 4 min, followed by a decrease from control of about 4%, sustained over a 32.5-min period of the drug test procedure. Similar changes, but of reduced magnitude and duration, were observed at a dose of 167 mg/kg. The 2-PMPA-induced decreases in BOLD signals appear to indicate that blood deoxyhemoglobin is elevated when endogenous NAAG cannot be hydrolyzed, thus linking the efflux of NAAG from neurons and its hydrolysis by astrocytes to hyperemic oxygenation responses in brain.

Anesthesia, General↗
PubMed2003

Quantitative measurements of proton spin-lattice (T1) and spin-spin (T2) relaxation times in the mouse brain at 7.0 T.

The goal of this work is to provide regional T(1) and T(2) values at a field strength of 7 T for the normal mouse brain at 6 weeks and 1 year old. A novel segmented snapshot FLASH sequence was used to measure T(1) in the hippocampus, corpus callosum, and the retrosplenial granular (RSG) cortex; T(2) measurements were made in the same regions using a single spin echo sequence repeated at six separate echo times. Both T(1) and T(2) measurements were validated with phantom measurements.

Age Factors↗
PubMed2003

Diffusion tensor imaging in fixed brain tissue at 7.0 T.

The purpose of this work is to assess the feasibility of performing quantitative in vitro brain tissue diffusion tensor imaging (DTI) measurements and to examine their comparability to in vivo measurements. DTI of fixed tissue at high field strength is potentially a very valuable investigative tool as very high spatial resolution can be achieved. DTI was applied to human and mouse brain fixed tissue samples as well as in vivo measurements of the mouse brain. T(1) and T(2) relaxography of the fixed tissue samples was also performed to provide further characterization of the tissue. All experiments were performed at 7 T. The fractional anisotropy (FA) of the human fixed brain tissue samples is found to be higher in the corpus callosum than in the occipital white matter region, consistent with in vivo measurements reported in the literature. Our FA measurements of the corpus callosum of a mouse brain are also found to be the same both in vitro and in vivo. This preliminary work supports the use of DTI in both fixed human and fixed animal brain tissue as a valid investigative tool. With the increased availability of brain banks in different brain disorders, DTI in fixed tissue may prove to be a very useful method for the study of white matter abnormalities.

Animals↗
PubMed2003

REST-PEEP: reduced scan time phase-encoded echo planar imaging.

Echo planar methodology can be used for rapid acquisition in three dimensions of k-space. There are two groups of sequences which have thus far been implemented. The first group is characterized by three-dimensional acquisition from a single RF excitation. Echo planar shift mapping and echo volume imaging are single-shot chemical shift imaging and three-dimensional spatial imaging techniques, respectively. Even though these methods are extremely fast, their spatial and spectral resolutions are poor. In the second group of sequences, echo planar imaging acquisition is repeated for every phase-encode gradient step to improve upon the spatial resolution and signal-to-noise ratio at the expense of acquisition time. Here we report a novel combination of these two groups of sequences aimed at providing additional flexibility in trade-offs between the spectral bandwidth, signal-to-noise ratio, spatial resolution and imaging time. Preliminary results for both chemical shift imaging and three-dimensional spatial imaging are presented. The chemical shift imaging was optimized for excitation of the N-acetyl aspartate (NAA). An interesting consequence of our approach is that the Nyquist ghost is transferred from the spectrum to the metabolite image.

Algorithms↗
PubMed2003

The apparent dependence of the diffusion coefficient of N-acetylaspartate upon magnetic field strength: evidence of an interaction with NMR methodology.

An inverse relationship between applied magnetic field strength and the apparent diffusion coefficient (ADC) of several important brain metabolites including N-acetyl-l-aspartate (NAA), choline and creatine, measured in vivo using proton magnetic resonance spectroscopy (MRS), has been reported. In this investigation, using phantom studies of NAA at magnetic field strengths of 3 and 7 T, these observations have been verified under controlled MRS conditions in vitro, and the ADC of NAA has been found to vary inversely with magnetic field strength, decreasing at a rate of 2.5%/T at 20 degrees C. We have also assessed whether the effect is a function of a systemic bias in methodology, or if the effect is actually on the rate of molecular diffusion. This was done using an MRS-independent method for measurement of molecular diffusion in NAA phantoms at 0, 0.025 and 7 T applied magnetic field strengths. As a result, it has been demonstrated that the observed apparent magnetic field dependence of the ADC of NAA is a consequence of the NMR measurement and is apparently not a real effect on molecular diffusion.

Artifacts↗
PubMed2003

In vivo NMR studies of neurodegenerative diseases in transgenic and rodent models.

In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide unique quality to attain neurochemical, physiological, anatomical, and functional information non-invasively. These techniques have been increasingly applied to biomedical research and clinical usage in diagnosis and prognosis of diseases. The ability of MRS to detect early yet subtle changes of neurochemicals in vivo permits the use of this technology for the study of cerebral metabolism in physiological and pathological conditions. Recent advances in MR technology have further extended its use to assess the etiology and progression of neurodegeneration. This review focuses on the current technical advances and the applications of MRS and MRI in the study of neurodegenerative disease animal models including amyotrophic lateral sclerosis, Alzheimer's, Huntington's, and Parkinson's diseases. Enhanced MR measurable neurochemical parameters in vivo are described in regard to their importance in neurodegenerative disorders and their investigation into the metabolic alterations accompanying the pathogenesis of neurodegeneration.

Animals↗
PubMed2002

Effect of N-acetylaspartic acid on the diffusion coefficient of water: a proton magnetic resonance phantom method for measurement of osmolyte-obligated water.

N-acetyl-L-aspartic acid (NAA) is an amino acid present in the vertebrate brain that is synthesized and stored primarily in neurons, although it cannot be hydrolyzed in these cells. Nonetheless, neuronal NAA is dynamic and turns over more than once each day by cycling, via extracellular fluids (ECF), between neurons and catabolic compartments in oligodendrocytes. One important role of the NAA intercompartmental cycle appears to be osmoregulatory, and in this role it may be the primary mechanism for the removal of metabolic water, against a water gradient, from myelinated neurons. However, the number of water molecules that might be cotransported to ECF per NAA molecule released is as yet unclear. In this investigation, using a proton nuclear magnetic resonance method and diffusion measurements at two magnetic field strengths on water and NAA phantoms in vitro, the effect of NAA on the diffusion coefficient of water has been measured, and a ratio (K) of obligated water molecules per molecule of NAA has been determined. For NAA measured at 100mM and 3 Tesla K=24 and at 7 Tesla K=14. Based on these results, apparent K(NAA) varies inversely with field strength, and with a computed field strength factor of 2.55mmol water/unit Tesla, K(NAA) in the absence of any applied magnetic field strength would be 32.

Aspartic Acid↗