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Biomedical subjects

Graeme F Mason

Publications and source records attributed to Graeme F Mason.

28 records · Page 2Linked to original sources

A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose.

13C-labeled glucose is increasingly used in conjunction with magnetic resonance spectroscopy to measure rates of metabolic pathways in the brain in vivo. Most studies of human subjects have used intravenous infusions to administer the labeled compounds, but the procedure is cumbersome and can be uncomfortable for patients with neurological or psychiatric disorders. It may be possible to improve the practicality of the method by administering the glucose orally instead of intravenously. This report describes the performance and comparison of the oral and intravenous protocols in the same subjects. The conclusion is that oral administration does yield the same result as intravenous administration but with lower precision. That sensitivity of the oral protocol may be improved by several ways that are available today.

Administration, Oral↗

Increased cortical GABA concentrations in depressed patients receiving ECT.

OBJECTIVE: Reduced gamma-aminobutyric acid (GABA) concentrations have been reported in the plasma, CSF, and cortex of depressed subjects. Of interest is that ECT, one of the most effective treatments for severe refractory depression, produces considerable anticonvulsant effects that may be related to increased GABAergic transmission. The purpose of this study was to determine if cortical GABA concentrations increase following a course of ECT. METHOD: Occipital cortex GABA concentrations in eight depressed patients were measured by using proton magnetic resonance spectroscopy before and after a course of ECT. RESULTS: A significant increase in occipital cortex GABA concentrations was seen following ECT treatment of depression. CONCLUSIONS: Occipital cortex GABA concentrations increase two-fold following ECT. This suggests possible GABAergic involvement in ECT's mechanism of anticonvulsant and antidepressant actions.

Anticonvulsants↗

Magnetic resonance spectroscopy for studies of neurotransmission in vivo.

Magnetic resonance spectroscopy (MRS) of hydrogen and carbon allow the study of neurochemical alterations in neuropsychiatric disorders. This paper discusses the basic theory of MRS in order to provide an understanding of this complicated technical area. A variety of applications of hydrogen MRS in the study of neuropsychiatric disorders are reviewed; these applications can generate useful hypotheses about brain metabolism. Following that is a description of neurotransmitter cycling and how kinetic carbon MRS can be used to extend hydrogen MRS measurements to evaluate the rate of cycling and energy metabolism. The remainder of the article focuses primarily on steps that are necessary for MRS to become more widely used, making it clinically viable and allowing the study of large populations.

Animals↗

Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism.

Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into brain glutamate and glutamine in eight volunteers during an intravenous infusion of [2-13C] acetate, which has been shown in animal models to be metabolized specifically in astroglia. Mathematical modeling of the three established pathways for neurotransmitter glutamate repletion indicates that the glutamate/glutamine neurotransmitter cycle between astroglia and neurons (0.32 +/- 0.07 micromol x gm(-1) x min(-1)) is the major pathway for neuronal glutamate repletion and that the astroglial TCA cycle flux (0.14 +/- 0.06 micromol x gm(-1) x min(-1)) accounts for approximately 14% of brain oxygen consumption. Up to 30% of the glutamine transferred to the neurons by the cycle may derive from replacement of oxidized glutamate by anaplerosis. The further application of this approach could potentially enlighten the role of astroglia in supporting brain glutamatergic activity and in neurological and psychiatric disease.

Acetates↗

Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study.

BACKGROUND: There is increasing support for the hypothesis that gonadal steroids involved in the regulation of the human menstrual cycle modulate gamma-aminobutyric acid (GABA) neuronal function. This study tests the hypothesis that cortical GABA neuronal function, reflected in brain GABA concentrations, fluctuates across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder (PMDD) and that a menstrual cycle phase-dependent abnormality in brain GABA concentrations in women diagnosed as having PMDD would reflect altered central response to circulating gonadal and neuroactive steroids. METHODS: Fourteen healthy menstruating women and 9 women diagnosed as having PMDD were recruited from a women's behavioral health research program located at a university-based medical center. The women underwent serial proton magnetic resonance spectroscopic measurements of occipital cortex GABA levels across the menstrual cycle (primary outcome measure) and had blood drawn for gonadal hormone and neurosteroid levels determined on each scan day (secondary outcome measure). RESULTS: There was a significant group x phase interaction with most of the finding explained by the reduction in cortical GABA levels during the follicular phase in those with PMDD compared with healthy controls. Cortical GABA levels declined across the menstrual cycle in healthy women, whereas women with PMDD experienced an increase in cortical GABA levels from the follicular phase to the mid luteal and late luteal phases. Significant between-group differences in the relationship between hormones and GABA were observed for estradiol, progesterone, and allopregnanolone. CONCLUSIONS: These data strongly suggest that the GABAergic system is substantially modulated by menstrual cycle phase in healthy women and those with PMDD. Furthermore, they raise the possibility of disturbances in cortical GABA neuronal function and modulation by neuroactive steroids as potentially important contributors to the pathogenesis of PMDD.

Adult↗

Graded image segmentation of brain tissue in the presence of inhomogeneous radio frequency fields.

Image segmentation is used increasingly to interpret MR spectroscopic data of the brain, using image contrast to identify gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF). T(1)- or T(2)-weighted images are typically used, but poor shimming, susceptibility effects, and small variations in B(1) and receptivity cause difficulties in tissue identification. Quantitative imaging of T(1) can reduce many of these difficulties but is still subject to complications when B(1) has large variations like those observed with the surface coils often used for spectroscopy. In this study, B(1) imaging was implemented to support quantitative imaging of T(1) with either a surface coil or a volume coil. The T(1) observed by this method is a continuous function across mixtures of WM/GM and GM/CSF, and this function was measured and used to convert the images of T(1) to maps of percent GM, WM, and CSF.

Brain↗

Regional cerebral blood flow and magnetic resonance spectroscopic imaging findings in diaschisis from stroke.

BACKGROUND AND PURPOSE: This study evaluated blood flow and metabolite changes in cerebral diaschisis from internal capsule region infarction using regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) and 1H magnetic resonance spectroscopic imaging (MRSI). We hypothesized that complementary measures of diaschisis effects in white matter (characterized by 1H MRSI) and gray matter (characterized by changes in rCBF) can be measured and exhibit parallel changes. METHODS: Five stroke patients and 16 normal controls underwent Tc-99m hexamethylpropyleneamine-oxime brain SPECT and 1H MRSI at 4.1 T. The metabolites N-acetyl aspartate (NAA) and creatine (Cr) were measured using 1H MRSI. The tissue content was expressed as the percent of gray or white matter in each MRSI voxel to allow comparison of the differential effects of diaschisis in gray and white matter tissue types. The blood flow and metabolite changes were evaluated at superior cerebral regions distant from the stroke to allow a measure of diaschisis relatively unconfounded by their expected changes in the infarction region. RESULTS: The rCBF SPECT data in stroke patients showed a perfusion defect, with size ranging from 1.23 cc to 10.23 cc, in the region of cortical diaschisis. 1H MRSI showed increased Cr/NAA ratios in regions of white matter diaschisis. There was a tendency for larger rCBF defect size to be associated with greater increases in Cr/NAA values in the same diaschitic cerebral hemisphere, ipsilateral to the infarction. CONCLUSION: Diaschisis ipsilateral to stroke in white matter can be characterized by 1H MRSI, and diaschisis ipsilateral to stroke in cortical gray matter regions can be characterized by changes in rCBF. The tendency for greater reductions in cortical rCBF values to be associated with increased Cr/NAA values in the same diaschitic cerebral hemisphere implies that a relationship exists between rCBF reductions in gray matter and abnormal changes in white matter subservient to it.

Adult↗

Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors.

OBJECTIVE: Studies have demonstrated low concentrations of gamma-aminobutyric acid (GABA) in the plasma and CSF of individuals with major depression, and low GABA concentrations have also been found in the occipital cortex of depressed subjects. The goal of this study was to determine whether these occipital cortex GABA concentrations are altered after administration of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. METHOD: By means of proton magnetic resonance spectroscopy, occipital cortex GABA concentrations were measured in 11 medication-free depressed patients before initiation of treatment with SSRI medications and after an average of 2 months of treatment. RESULTS: A significant increase in occipital cortex GABA concentrations was seen after SSRI treatment. CONCLUSIONS: SSRI treatment of major depression is associated with increased occipital cortex GABA concentrations. This appears to result in a normalization of low pretreatment GABA concentrations, an effect that may contribute to a common mechanism of antidepressant action.

Adult↗

In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism.

13C NMR spectroscopy in combination with the infusion of (13)C-labeled precursors is currently the only technique that is capable of quantitatively studying energy metabolism, neurotransmission and other metabolic pathways non-invasively in vivo. (1)H-[(13)C]-NMR spectroscopy is a high-sensitivity alternative to direct (13)C NMR spectroscopy. The development of improved NMR methods for water suppression, spatial localization, broadband decoupling, shimming and signal quantification, together with the availability of high magnetic field strengths, has made (1)H-[(13)C]-NMR spectroscopy the method of choice for the detection of metabolism at a high spatial and/or temporal resolution. (1)H-[(13)C]-NMR spectroscopy can now be used to discriminate glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activity. The improved sensitivity allows the detection of metabolism in different tissues (e.g. gray and white matter) and potentially even in smaller structures, like cortical layers. Finally, (1)H-[(13)C]-NMR spectroscopy allows the detection of energy metabolism and neurotransmission during functional activation, thereby further strengthening our understanding of the neurochemical basis of brain function.

Algorithms↗