Metabolite specific proton magnetic resonance imaging.

Abstract

An imaging method is described that makes use of proton double quantum nuclear magnetic resonance (NMR) to construct images based on selected metabolites such as lactic acid. The optimization of the method is illustrated in vitro, followed by in vivo determination of lactic acid distribution in a solid tumor model. Water suppression and editing of lipid signals are such that two-dimensional spectra of lactic acid may be obtained from a radiation-induced fibrosarcoma (RIF-1) tumor in under 1 min and lactic acid images from the same tumor in under 1 hr at 2.0 T. This technique provides a fast and reproducible method at moderate magnetic field strength for mapping biologically relevant metabolites. This paper describes an efficient proton nuclear magnetic resonance (NMR) imaging method that can be used to noninvasively map the distribution and levels of certain biologically significant metabolites in vivo. Metabolites of clinical interest include lactic acid (1), N-acetylaspartate (2), alanine (3), and taurine (4). Lactate was chosen for these initial studies because of its biochemical and pathological importance. An elevated level of tissue lactate may indicate (i) the presence of hypoxia, characterized by an increased rate of anaerobic glycolysis, as is found in certain solid tumor centers; (ii) conditions of reduced blood flow (ischemia), such as occurs in coronary infarct and cerebral stroke; (iii) certain inborn errors of metabolism-for example, pyruvate dehydrogenase and pyruvate carboxylase deficiency, or (iv) diabetes (type I)-in which oral phenformin overdose might be implicated.To generate an in vivo proton magnetic resonance image based on a metabolite such as lactate requires the elimination, or reduction, of signals from the large population of water and lipid protons present in vivo, as well as separation of metabolites, residual water, and residual lipid signals. Because metabolite concentrations and magnetic field strength are the limiting factors for in vivo studies, the method must maintain a high level ofefficiency in terms ofselectivity, sensitivity, and minimum data acquisition time. In a previous study (5), two-dimensional double quantum coherence transfer spectroscopy (Fig. 1A) was used to determine steady-state lactate levels in vivo (Fig. 1B). Because of high residual water and lipid levels observed in data collected by the method shown in Fig. 1, both the double quantum (w1) and chemical shift (w2) dimensions are needed for spectral editing. This means that a four-dimensional matrix would be required to obtain an image based on this method.For practical in vivo imaging, the aim was to eliminate the requirement for the chemical shift (W2) dimension by improving the performance of the double quantum method. The w2 dimension can then be used for encoding space rather than chemical shift.The efficiency and limits of detection of double quantum coherence methods were evaluated by using aqueous solutions of lactic acid or its NMR analogue N-acetyl alanine. Metabolite specific images usin...

In vivo GABA editing using a novel doubly selective multiple quantum filter

“…The advantage of the current doubly selective multiple quantum preparation method over the nonselective or semiselective methods is that the suppression of glutathione is achieved using gradient filtering, which is more effective than RF selectivity alone. On the other hand, the method proposed here should be easily adapted for selective measurement of other J-coupled metabolites such as glutathione (18), lactate (29,30), ␤-hydroxybutyrate (29,31), and glutamate/glutamine.…”

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo 13C MRS

“…For more than 70 years, it has been known that cancer cells utilize and metabolize glucose at high rates, even in the presence of high oxygen concentrations, to form mainly lactate (36). Indeed, lactate was found to be present in tumors at levels much higher than in the corresponding normal tissues (9,15,16,25). Furthermore, quantitative studies of biopsies from human cancers have indicated a positive correlation between tumor lactate concentration and incidence of metastasis (5,26,34,35).…”

Lactate discrimination incorporated into echo‐planar spectroscopic imaging

“…These techniques demonstrate the efficiency of lactate discrimination, but there remain some disadvantages with regard to measurement time and to obtaining the spectra of other metabolites. At least two measurements are generally required for selective irradiation, spectral editing, or polarization transfer (3-5,9); and images of other metabolites cannot be acquired simultaneously when multiple quantum coherence are used (7,8). Although the spectral editing technique using multi-spin-echo allows the images of the other metabolites to be simultaneously acquired in a single measurement, sufficient discrimination is sometimes not provided by the T 2 variation of the lipid signal (6).…”

“…Additional discrimination of the lactate signal from the lipid signal is therefore of great benefit for obtaining accurate lactate images, and several lactate-discriminating techniques have been reported that use the difference between the relaxation times of lactate and lipid (1,2) or homonuclear coupling in lactate protons (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Application to spectroscopic imaging has also been described (2)(3)(4)(5)(6)(7)(8). The lactate-discriminating techniques using homonuclear coupling can be classified as four kinds: selective irradiation (3), spectral editing (4 -6), multiple quantum coherence (7,8), and polarization transfer (9).…”

“…Application to spectroscopic imaging has also been described (2)(3)(4)(5)(6)(7)(8). The lactate-discriminating techniques using homonuclear coupling can be classified as four kinds: selective irradiation (3), spectral editing (4 -6), multiple quantum coherence (7,8), and polarization transfer (9). These techniques demonstrate the efficiency of lactate discrimination, but there remain some disadvantages with regard to measurement time and to obtaining the spectra of other metabolites.…”