Abstract Positron emission tomography (PET) is increasingly used to quantify regional hemodynamic and metabolic changes in different animal models. Most of these (multitracer) studies provided important early data on already functionally altered brain tissue, indicating selective vulnerability by a large variability in the functional blood flow threshold of individual neurons. To fill the gap between experimental studies at early time points and rather late clinical studies at well-defined but singular time points, we repeatedly measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction rate and cerebral metabolic rate of glucose (CMR glc) in three cats before and up to 28 h after decompressive hemicraniectomy on normal brain tissue. Decompressive hemicraniectomy in the cat decreased CBF, and to a lesser extent CMRO2 and CMR glc 2 h after surgical intervention in normal brain tissue that last for at least 1 day. CBF significantly decreased ( p<0.01) and oxygen extraction fraction (OEF) ( p<0.05) significantly increased. CMRO2 and CMR glc decreased only in regions with most severe CBF reduction. These effects remained for at least a day irrespective of corrective sustaining cranioplasty. The method and data analysis is decreased and discussed in detail in the presented protocol. In conclusion, serial positron emission tomography studies are best suited to repeatedly and non-invasively demonstrate circulatory and biochemical changes by surgical interventions in normal brain tissue for at least one day. The transition of normal brain tissue into misery-perfused or non-viable regions can be followed over time. Such state-of-the-art imaging modalities as sequential high-resolution positron emission tomography provide insight into the dynamic of regional pathophysiology and may thus further justify the development of rational therapeutic strategies for decompressive hemicraniectomy, especially for disease with focal disturbances in cerebral blood flow.