Measurement of human tricarboxylic acid cycle rates during visual activation by (13)C magnetic resonance spectroscopy.

Measurement by (13)C magnetic resonance spectroscopy (MRS) of the incorporation of label from [1-(13)C] glucose, initially into C4 of glutamate, allows the regional tricarboxylic acid (TCA) cycle flux (F(TCA)) to be determined in the human brain. In this study, a direct (13)C MRS approach was used at 3T, with NOE enhancement and (1)H decoupling with WALTZ16, to determine basal F(TCA) in six volunteers. The values found in the visual cortex are similar to those reported in previous (13)C MRS studies, and consistent with PET measurements of the cerebral metabolic rate for glucose, CMRglc. In two preliminary activation studies using light emitting diode (LED) goggles flashing at 8 Hz, compared to darkness as control, increases in F(TCA) were found from 0.60 +/- 0.10 to 0.94 +/- 0.03 micromol/min/g (56%) and from 0.34 +/- 0.14 to 0.56 +/- 0.07 micromol/min/g (65%). These are upper estimates, but they are similar to the increases in CMRglc reported in PET studies, and strongly suggest, in contrast to these PET studies, that cerebral glucose is metabolized oxidatively, even during intense visual stimulation. This is supported by the observation that very little (13)C label is incorporated into C3 lactate, as would be expected if glucose were metabolized anaerobically. There is evidence for incorporation of glucose into cerebral glycogen, but this is a relatively minor component of cerebral glucose metabolism.

An integrated strategy for evaluation of metabolic and oxidative defects in neurodegenerative illness using magnetic resonance techniques.

The number of physiologic and metabolic phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. MR techniques can now evaluate tissue parameters relevant to TCA cyclemetabolism, anerobic glycolysis, ATP levels, blood-brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood flow and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iron concentrations. In addition to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding; and in addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of water diffusion. A strategy for integration of these multifarious parameters in a comprehensive neurofunctional exam in neurodegenerative illness is outlined in this paper. The goals of the integrated exam, as applied to a given neurodegenerative illness, can be subdivided into three categories: etiology, natural history, and therapeutic end points. The consequences of oxidative stress and/or mitochondrial dysfunction are explored in the context of the various parameters that can be measured using the integrated MR exam.

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.