New MRI measure maps blood flow and cellular organization

Researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have developed a new, noninvasive way to examine how blood flow and cellular organization align across the layers of the living human brain.

The cerebral cortex, the brain's folded outer layer, contains layers with different numbers and types of cells. These cells need a continuous supply of oxygen and nutrients, but researchers have had limited tools for studying how blood flow matches their distribution in the living brain.

"The brain has almost no ability to store energy, so its cells depend on a constant and carefully regulated supply from the bloodstream," said Fanhua Guo, co-first author of the study and a researcher at the Stevens INI. "Our new measure gives us a way to study how well that energy supply is positioned to meet cellular demands in different parts of the cortex."

Mapping blood flow across cortical layers

The researchers used arterial spin labeling, or ASL, a noninvasive MRI technique that magnetically labels water in the blood and tracks it into brain tissue. A powerful 7 Tesla MRI scanner measured blood flow throughout the brain at a resolution of one cubic millimeter. The study included 30 healthy adults; 14 returned for a second scan to test the consistency of the measurements.

The team divided the cortex into 360 regions and examined blood flow at multiple depths. They compared those patterns with cell-body staining data from BigBrain, a detailed three-dimensional digital reconstruction of a human brain that maps how densely cells are packed throughout the cortex.

"Conventional brain imaging often averages information across the full thickness of the cortex, but the cortex is not a uniform sheet," said Chenyang Zhao, co-first author of the study and a researcher at the Stevens INI. "By imaging blood flow at very high resolution, we can begin to see how perfusion changes from the outer surface of the cortex to its deeper layers."

The resulting CCSI score measured how closely blood flow and cellular density followed the same pattern across cortical depth. Higher scores indicated that cell-dense layers tended to receive more blood flow. Blood flow and cellular organization aligned in most cortical regions, meaning that within a given region, blood flow tended to be highest in the layers with the most cells, although the strength varied across the brain. Alignment was strongest in primary visual and sensorimotor areas, which support vision, movement, and touch.

Connecting blood flow to the brain's energy system

To clarify what CCSI represents biologically, the researchers compared it with maps of mitochondrial activity, cell types, and gene expression.

Mitochondria convert nutrients and oxygen into usable energy. Regions where blood flow and cellular organization aligned more strongly also had greater mitochondrial respiratory capacity, the maximum rate at which mitochondria can produce energy, suggesting they may be better equipped to meet local energy demands.

The relationship involved mitochondrial capacity, not simply the number of mitochondria. Total blood flow did not show the same association, suggesting CCSI reveals metabolic organization that standard blood-flow measurements may miss.

CCSI was also associated with capillary endothelial cells, which line the smallest blood vessels and help regulate how blood reaches surrounding tissue. It was also associated with mature oligodendrocytes, brain cells that produce the protective myelin coating around nerve fibers. Because oligodendrocytes also support nerve fibers' metabolism, the finding suggests they may help connect vascular supply with neurons' energy needs.

Gene activity further linked CCSI to energy metabolism, blood vessel development, vascular organization, and healthy mitochondria. Together, the findings suggest that the alignment of blood flow and cellular structure reflects a coordinated system involving blood vessels, supporting cells, and energy production.

Helping explain the brain's most complex regions

The researchers also asked whether CCSI could help explain the relationship between brain structure and function. That connection is usually close in sensory and motor regions but less direct in higher-order association regions, which support memory, reasoning, and attention.

The study does not establish that stronger alignment causes more efficient energy use. Its molecular and cellular comparisons relied on reference atlases from a limited number of postmortem donors, and CCSI currently measures groups rather than individuals. Future studies will test larger, more varied populations and explore changes linked to aging and neurological or psychiatric conditions.

Disruptions in blood flow, metabolism, and oligodendrocyte function occur in Alzheimer's disease, multiple sclerosis, schizophrenia, and epilepsy. CCSI could eventually help researchers study how these systems become disconnected.

Source:

Keck School of Medicine of USC

Journal reference: