Quantification of human high-energy phosphate metabolite concentrations at 3 T with partial volume and sensitivity corrections

Abstract

Practical noninvasive methods for the measurement of absolute metabolite concentrations are key to the assessment of the depletion of myocardial metabolite pools which occurs with several cardiac diseases, including infarction and heart failure. Localized MRS offers unique noninvasive access to many metabolites, but is often confounded by nonuniform sensitivity and partial volume effects in the large, poorly defined voxels commonly used for the detection of low-concentration metabolites with surface coils. These problems are exacerbated at higher magnetic field strengths by greater radiofrequency (RF) field inhomogeneity and differences in RF penetration with heteronuclear concentration referencing. An example is the (31)P measurement of cardiac adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations, which, although central to cardiac energetics, have not been measured at field strengths above 1.5 T. Here, practical acquisition and analysis protocols are presented for the quantification of [PCr] and [ATP] with one-dimensionally resolved surface coil spectra and concentration referencing at 3 T. The effects of nonuniform sensitivity and partial tissue volumes are addressed at 3 T by the application of MRI-based three-dimensional sensitivity weighting and tissue segmentation. The method is validated in phantoms of different sizes and concentrations, and used to measure [PCr] and [ATP] in healthy subjects. In calf muscle (n = 8), [PCr] = 24.7 ± 3.4 and [ATP] = 5.7 ± 1.3 µmol/g wet weight, whereas, in heart (n = 18), [PCr] = 10.4 ± 1.5 and [ATP] = 6.0 ± 1.1 µmol/g wet weight (all mean ± SD), consistent with previous reports at lower fields. The method enables, for the first time, the efficient, semi-automated quantification of high-energy phosphate metabolites in humans at 3 T with nonuniform excitation and detection.

Keywords: 3 T; high field; human heart; metabolism; phosphorus; quantification.

Figure 1

Flow chart of the principal acquisitions (green shading), data analysis (pink shading) and calculations required to measure metabolite concentrations via the described MRS method. Alpha-numeric labels in blue correspond to the acquisition/analysis steps described in the “Methods” section.

Figure 2

Annotated screen photograph of the PC-based user analysis software as applied to the segmentation of cardiac MRIs (top right and below) and computing [PCr] and [ATP] from ³¹P 1D CSI spectra (list, lower right).

Figure 3

(a) Calculated concentration for a 5.7cm diameter cylindrical phantom filled with 5 (green filled circles), 10 (black crosses), 20 (red squares) and 30 (blue empty circles) mM of NaH₂PO₄, as a function of depth. (b) Mean±SD phosphate concentrations as a function of true concentration for the 3.7 cm (“small”; black squares), 5.7 cm (“medium”; red crosses) and 9.4 cm (“big”; blue circles) diameter cylinder phantoms. The hashed lines indicate actual concentrations in (a), and identity in (b).

Figure 4

[PCr] and [ATP] (mean±SD) measured in the calf muscle of 8 volunteers, as a function of depth. The sample size (n) varies with depth due to different leg sizes.

Figure 5

Axial heart image showing 1DCSI planning (top left) and corresponding cardiac spectrum from slice 7. The spectrum is a 1D projection of the real component of the 3D plot fitted using the “circle fit” software routine without baseline correction (22).