Non-invasive imaging of brain function and energy supply is crucial for diagnosing and treating brain disorders. Conventional imaging struggles to capture altered relationships between energy supply and utilization caused by brain diseases. A novel method, which can be translated to human patients, is to calculate relative power (rPWR) and relative cost (rCST) to assess cerebral energy efficiency. However, whether rPWR/rCST can track individual changes and neural activity remains unproven. Our study compared these non-invasive measures with invasive two-photon microscopy in awake and anesthetized mice. We found that rPWR/rCST distributions were similar between awake mice and humans, but changed in anesthetized mice, indicating a shift in the brain’s economic balance. Furthermore, changes in rPWR/rCST were linked to the reorganization of microscopic neural networks, observed with two-photon microscopy. Our work highlights the potential of rPWR/rCST for medical applications, and that neural network reorganization is linked to the brain’s economic balance.