INTRODUCTION: Despite recent advances in measuring ATP energy metabolism using ³¹P magnetization transfer (MT)^1-3, there is still a lack of localized techniques capable of assessing the regional ATP synthesis, especially in the human brain. The importance of measuring regional ATP rates and fluxes in the human brain is highlighted by the heterogeneity in normal brain functions and also in many cerebral metabolic abnormalities such as cancers, ischemic injuries and a wide range of neurodegenerative diseases⁴. In this study, we demonstrate that, by combining wide-band inversion transfer⁵ with image selected in vivo spectroscopy (ISIS)⁶, quantitative information regarding ATP synthesis reaction Pi ==> γ-ATP can be obtained from the localized regions in the human brain.

METHODS: A short adiabatic pulse was used to co-invert ATP and PCr signals, followed by a varying delay time to buildup MT effect between Pi and g-ATP. Single-voxel or 2D ISIS ³¹P MR spectra were collected from occipital and parietal regions with constant TRs (5 sec for single-voxel, and 3 sec for 2D ISIS). The experiments were conducted on a 7T whole-body scanner with a partial volume double-tuned ¹H /³¹P T/R coil. Five subjects (3 females and 2 male) participated this study with written consent under an approved IRB protocol.

RESULTS and DISCUSSION: As shown in the single-voxel (Fig. 1) and 2D (Fig. 2) ISIS ³¹P spectra, all major ³¹P metabolites involved in MT are well resolved, with sufficient SNRs for detecting MT effect following band inversion and the subsequent delays. A typical Pi reduction of 20% - 30%, originated from MT effect between Pi and g-ATP, is clearly measurable under the experiment conditions, corresponding to an ATP synthesis rate constant of 0.20 ± 0.04 sec^-1, or ATP synthesis flux of 9.6 ± 1.9 mM/min, in resting human brain. The adoption of band inversion transfer technique4 in this study is due to the improved transfer efficiency, reduced RF exposures and minimized MT artifacts, as compared to more commonly used saturation transfer. These factors are particularly important for brain studies given its small tissue size and more tightened SAR restriction.

CONCLUSIONS: Band inversion in combination with ISIS allows the assessment of ATP synthesis in relative large voxels (~8 cc) of the selected regions in the human brain. The technique is expected to be especially useful in studies of ATP metabolism in many brain disorders with regional heterogeneities.