Quantitative imaging of energy expenditure in human brain

Abstract

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo(31)P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMR(ATPase)) and creatine kinase (CMR(CK)), and to determine CMR(ATPase) and CMR(CK) in pure gray mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMR(CK) is seven times higher than CMR(ATPase) in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo(31)P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function.

Figure 1

Measurement of in vivo ³¹P-MT CSI of Human Brain at 7T. Global in vivo ³¹P MR spectra (4 signal averages and TR = 7.1 s) acquired from a representative human brain in the (a) absence (control) and (b) presence (saturation) of γ-ATP. The arrows indicate the saturation site and the shaded areas are the chemical shift range for displaying the ³¹P-MT CSI spectra used in (d) and (e). (c) A ¹H anatomic image and the corresponding 2D ³¹P-MT CSI slice taken from the 3D data set (TR=0.73 s; 47.3 min data acquisition) from the same subject at control (d) and saturation (e) conditions, respectively. A typical ³¹P-MT CSI spectrum from a grey-matter dominated voxel (cylindrical voxel shape with actual size of 10.9 ml and nominal size of 2.3 ml) defined by the white circle in (c) at control (f) and saturation condition (g). The solid arrows point to the signal reductions of PCr and Pi compared to the control spectrum due to the chemical exchange and MT effects.

Figure 2

Three-dimensional Imaging of CMR_ATPase and CMR_CK in GM- and WM-like VOIs. (a) ³¹P-MT spectra of GM-like (left panel) and WM-like (right panel) VOIs from a representative subject's brain. Each VOI contains eight individual voxels located in either grey-matter or white-matter dominated brain regions; and each ³¹P spectrum is the sum of eight spectra from the corresponding voxels of the 3D-CSI data. (b) Segmented ¹H MR images of the same subject's brain. Different tissue types, i.e. grey-matter (in light grey color), white-matter (in white color) and CSF (in dark grey color) are identified and displayed in the composition images. The selections of GM-like VOI (black circles in top row) and WM-like VOI (grey circles in bottom row) are also illustrated.

Figure 3

Simulation Results in Determining T₁^nom Values for ATPase and CK Reactions. Simulation (open symbols) and linear regression (dash lines) of the magnetization ratio (M_c/M_s) vs. forward rate constant (k_f) for the CK reaction (a) and ATP_ase reaction (b) based on the Bloch-McConnell equations and known values of TR (0.73s), flip angle (36°) and intrinsic T₁ of PCr (4.9s) and Pi (3.7s). The correlation coefficients for both cases are close to 1 (R²>0.999). The slopes (T₁^nom) are 3.10s and 2.45s for PCr and Pi, respectively.

Figure 4

Quantification of CMR_ATPase and CMR_CK in Human GM and WM. Linear regression to determine the CMR_CK and CMR_ATPase values in pure GM and WM tissues of the human brain. The values are 68.8±13.3 and 22.2±7.5 μmol/g/min for CMR_CK,GM and CMR_CK,WM, 9.5±3.4 and 3.0±2.3 μmol/g/min for CMR_ATPase,GM and CMR_ATPase,WM, respectively.