Two distinct arterial spin labeling magnetic resonance imaging sequences generated contrasting age-related differences when measuring water exchange rates across the blood-brain barrier, according to a comparative neuroimaging investigation published in Fluids and Barriers of the CNS. The research team evaluated diffusion-weighted and multi-echo arterial spin labeling MRI to assess how each modality quantifies the blood-brain barrier water exchange rate in younger and older healthy adult cohorts across multiple anatomical brain regions.

Water exchange rate across the blood-brain barrier, denoted as Kw, has emerged as a promising candidate biomarker for studying brain aging and neurological disease. To compare the performance of diffusion-weighted and multi-echo arterial spin labeling in assessing this physiological parameter, the investigators recruited 12 young healthy participants aged 21 to 30 years, with a mean age of 26 ± 3 years, including 8 females, and 18 older healthy participants aged 66 to 84 years, with a mean age of 75 ± 7 years, including 13 females.

All study participants completed imaging protocols on a 3T MRI scanner that included diffusion-weighted arterial spin labeling, multi-echo arterial spin labeling, and structural T1-weighted scans. From these acquisitions, the researchers generated quantitative maps of Kw, arterial transit time, and cerebral blood flow. These parametric maps were linearly registered to the structural images and subsequently segmented using FreeSurfer into regional masks spanning 35 bilateral gray matter regions to extract localized measurements.

Statistical evaluations of global and regional metrics between the younger and older cohorts relied on mixed-effect linear regression models and two-sample t-tests with false discovery rate correction. In addition, the investigators conducted linear regression analyses to examine direct correlations between the two arterial spin labeling methodologies for cerebral blood flow, arterial transit time, and blood-brain barrier water exchange rate measurements.

Across the comparisons, cerebral blood flow showed a strong positive association between diffusion-weighted and multi-echo arterial spin labeling, with beta = 1.15 and p < 0.001. Arterial transit time also exhibited a moderate positive association between the two techniques, with a coefficient of beta = 0.46 and p < 0.001, demonstrating alignment between the two sequences for these perfusion metrics.

In marked contrast, blood-brain barrier water exchange rate measurements demonstrated an inverse relationship between the two acquisition methods, showing a negative association with beta = -0.62 and p < 0.001. The two sequences yielded opposite age-group differences in Kw across the whole brain and throughout all four cerebral lobes, while multi-echo arterial spin labeling consistently recorded substantially higher absolute Kw values than diffusion-weighted arterial spin labeling.

Regional analyses further demonstrated that multi-echo arterial spin labeling detected significantly higher water exchange rates in older adults within several specific anatomical areas. These included the medial orbitofrontal, inferior frontal, anterior cingulate, inferior temporal, transverse temporal, sensorimotor, and insular regions, identifying a greater total number of statistically significant regional age-group differences than diffusion-weighted arterial spin labeling.

The study authors concluded that diffusion-weighted and multi-echo arterial spin labeling detect distinctive patterns of blood-brain barrier Kw variation between young and older adults, highlighted by differing absolute values and opposite age-group directions. The authors emphasized that further validation is necessary to determine the precise physiological and experimental contexts in which these two MRI techniques serve as interchangeable or complementary quantitative markers of blood-brain barrier water exchange.

Subject of Research: Comparison of diffusion-weighted and multi-echo arterial spin labeling MRI for measuring blood-brain barrier water exchange

Article Title: Comparison of blood-brain barrier water exchange rate in young and older adults with diffusion-weighted and multi-echo arterial spin labeling MRI

Article References: Zhu, Y. D., Bhattarai, A., Albuhwailah, B., Shao, X., Petr, J., Eickel, K., Günther, M., Wang, D. J. J., & Fan, A. P. (2026). Comparison of blood-brain barrier water exchange rate in young and older adults with diffusion-weighted and multi-echo arterial spin labeling MRI. Fluids and Barriers of the CNS. https://doi.org/10.1186/s12987-026-00856-9

Image Credits: AI Generated

DOI: 10.1186/s12987-026-00856-9

Keywords: Blood-Brain Barrier, Arterial Spin Labeling, Magnetic Resonance Imaging, Aging, Water Exchange Rate, Cerebral Blood Flow, Arterial Transit Time, Neuroimaging, Comparison, blood-brain, barrier, water