Dynamic DWI detects respiratory modulation of brain parenchymal hydrodynamics

The circulation of cerebrospinal fluid (CSF) within the brain parenchyma and its exchange with interstitial fluid (ISF) are essential for maintaining homeostasis and clearing interstitial waste. However, the physiological forces driving parenchymal hydrodynamics remain unclear. Cardiac pulsation alone may be insufficient to drive parenchymal flow, while respiration has emerged as an additional contributor. To date, however, most respiration-related studies have focused on the ventricular system and spinal canal, leaving its influence on parenchymal hydrodynamics-the site of waste production-largely unexplored. In this study, we investigated whether parenchymal hydrodynamics are coupled with respiration during normal breathing, and how this coupling compares with that driven by cardiac pulsation. We used dynamic diffusion-weighted imaging (dynDWI) with a b-value of 150 s/mm² to capture incoherent fluid motion, quantified using the apparent diffusion coefficient (ADC). Respiration and cardiac signals were simultaneously recorded using a respiratory belt and finger photoplethysmography (PPG). Temporal coupling strength and time delay between parenchymal hydrodynamics and physiological signals were assessed using TRACC-PHYSIO (Time-domain Resolution-Aligned Cross-Correlation) for physiological coupling. We found that temporal ADC fluctuations in the parenchyma were coupled to respiration, with a latency of 0.7 seconds, and exhibited a gray-to-white matter propagation pattern. Spatial coupling patterns differed between respiration and cardiac pulsation: respiration coupling was stronger in gray and white matter than in the perivascular subarachnoid space (PVSAS) and lateral ventricles (LV), whereas cardiac coupling predominated in the PVSAS and LV. Rebinning dynDWI into respiration cycles revealed parenchymal ADC peaked during inhalation and reached a minimum during exhalation. Together, these findings suggest that respiration contributes to driving parenchymal hydrodynamics and fluid-driving forces vary spatially across brain regions, with respiration and cardiac pulsation playing complementary roles in regulating brain fluid dynamics.