New MRI Index Reveals How Brain Blood Flow Supports Cellular Energy Needs

The human brain has minimal energy reserves and relies on tightly regulated blood flow to meet its high metabolic demands. However, clinicians have lacked noninvasive tools to assess how cortical perfusion aligns with the cellular layers driving those demands, limiting insight into disorders such as Alzheimer’s disease, multiple sclerosis, schizophrenia, and epilepsy. Researchers have now developed an MRI measure that maps the relationship between blood flow and laminar cellular density across the human cortex.

The Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC (Los Angeles, CA, USA) has introduced the cerebral blood flow–cell-body staining intensity similarity index (CCSI). CCSI quantifies how closely perfusion patterns match cytoarchitecture across cortical depth. It leverages arterial spin labeling magnetic resonance imaging, performed on a 7 Tesla scanner at one-cubic-millimeter resolution, and compares perfusion profiles with cell-density maps from the BigBrain three-dimensional human brain atlas. The cortex was parcellated into 360 regions to evaluate laminar alignment.

The study enrolled 30 healthy adults; 14 underwent repeat scanning to assess measurement consistency. Higher CCSI scores indicated that cell-dense layers within a region received proportionally greater blood flow. Alignment between perfusion and cellular organization was observed across most cortical regions and was strongest in primary visual and sensorimotor areas that support vision, movement, and touch. These observations suggest a regionally varying coupling between vascular supply and cellular demand.

Biological context for CCSI was explored by comparing it with maps of mitochondrial activity, cell types, and gene expression. Regions with stronger alignment showed greater mitochondrial respiratory capacity, indicating better support for local energy needs, and this relationship was not explained by total blood flow alone. CCSI was associated with capillary endothelial cells and mature oligodendrocytes, and gene activity linked to energy metabolism, vascular development, vascular organization, and healthy mitochondria.

Adding CCSI to structural-functional coupling models significantly improved predictions of function in higher-order association regions that support memory, reasoning, and attention. The findings were published in Nature Communications. The study does not establish causality, relied on reference atlases from a limited number of postmortem donors, and currently evaluates groups rather than individuals. Future work will expand to larger, more diverse cohorts and probe aging and neurological or psychiatric conditions.

“Blood flow tells us how much blood reaches a region, but it does not tell us how that supply is distributed in relation to the cells that need it. CCSI adds that missing spatial information and may provide a more biologically meaningful picture of how vascular supply supports energy use across cortical layers,” said Danny JJ Wang, Ph.D., senior and corresponding author of the study, professor of neurology and director of imaging technology innovation at the Stevens INI.

“Understanding the healthy relationship between vascular supply and cellular organization is an important first step. The long-term goal is to determine whether changes in this relationship can reveal early signs of disease or help us evaluate treatments aimed at restoring brain metabolism and vascular health. The hope is that CCSI may eventually offer insight into early signs of disease and potential treatments,” stated Neda Jahanshad, Ph.D., professor of neurology and biomedical engineering at the Stevens INI.

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