Shou, Q. | bioRxiv Science

bioRxiv2024

Age-Related Decline in BBB Function is More Pronounced in Males than Females

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders. Significance statementThe blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.

neuroscience↗

bioRxiv2021

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling technique at 7T that offers the unique capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is [~]100 msec shorter than in middle/deep layers revealing the dynamics of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). We further demonstrated that top-down attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while bottom-up stimulus driven activity peaked in the middle layers (feedforward thalamic input). These quantitative laminar profiles of perfusion activity suggest an important role of M1 superficial layers for the computation of finger movements, and that visual attention may amplify deep layer output to the subcortex. Significance StatementCBF or microvascular perfusion measured by arterial spin labeling (ASL) is a key parameter for in vivo assessment of neurovascular function. Compared to BOLD or VASO fMRI, ASL perfusion contrast offers the unique capability for quantitative CBF measurements both at baseline and during task activation, which is critical for quantitative estimation of metabolic activities tightly related to neuronal activation. We proposed a zoomed 3D ASL technique at 7T for laminar perfusion imaging with high spatial specificity and sensitivity. This technique is able to differentiate and quantify the input/output and feedforward/feedback activities of human motor and visual cortex, thereby providing an important tool for quantitative assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

neuroscience↗