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 31P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMRATPase) and creatine kinase (CMRCK), and to determine CMRATPase and CMRCK in pure grey 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 CMRCK is seven times higher than CMRATPase 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 31P 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.

Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis

“…This suggests that 1% additional ATP generated by glycolysis comes at a price of 50% reduction of total ATP produced, which is unlikely because the V ATP from the present PET measurements is in good agreement with previous 31 P and 13 C MRS measurements in the awake resting human brain. [10][11][12][13] The agreement between PET and MRS measured values of V ATP suggests that there is negligible mitochondrial uncoupling in young healthy brain, but which may be altered during the course of healthy aging process. 30 Because the gray matter thickness of gyri and sulci is less than optimal for the spatial resolution of the PET Tables S1 and S2 for description of regions and networks ( Figure S1).…”

Mitochondrial Dysfunction in Autism Spectrum Disorders

“…As the site of energy generation, they are deemed the "powerhouse" of the cell and are responsible for providing cells with energy to function. Mitochondria are especially important in areas of high energy demand such as the brain where neuronal cells utilise an estimated 4.7 billion ATP per second [6]. ATP generation takes place through three major processes; glycolysis which takes place in the cytosol, tricarboxylic acid (TCA) cycle in the mitochondrial matrix and the electron transport chain (ETC) in the inner mitochondrial membrane.…”

Mitochondrial Trafficking in Neurons

“…This influx will require comparable millions of ATP to be hydrolyzed to pump the ions back across the plasma membrane. With hundreds or thousands of synapses impinging on a cell, it is easy to see why a recent imaging study determined that a resting cortical neuron consumes 4.7 billion ATP molecules per second (Zhu et al 2012). It is not only the synapses that consume energy; action potentials also require ATP to restore ion gradients, axonal transport is energy intensive, and, of course, there are all the "normal" requirements of a cell.…”