Abstract
The glymphatic-meningeal pathway, important for brain homeostasis, depends on the drainage function of the cervical lymphatic system. Although new therapies aim to modulate this pathway, a lack of methods for quantifying lymphatic drainage function hinders our ability to understand how targeting the cervical lymph nodes may benefit brain health. To address this, we developed and applied a fluid transport model to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data to visualize and quantify tracer-tagged lymph through the deep cervical lymph nodes (dcLN). The model incorporated physical principles of solute transport to provide a biologically interpretable framework for analyzing microflows in real-time. We applied this model to investigate the effects of chronic hypertension on dcLN drainage by comparing normotensive Wistar-Kyoto rats with spontaneously hypertensive stroke-prone (SHRSP) rats. In normal rats, the model revealed complex and tortuous lymph streams, of a 200 kDa tracer transported through the sinus system of the dcLN. In contrast, SHRSP rats exhibited significantly altered fluid dynamics, characterized by simpler stream patterns and reduced flow through the dcLN. These findings demonstrated that untreated chronic hypertension adversely affects lymph node drainage function. This provides new insight into impaired lymphatic drainage as a mechanism linking systemic disease to brain health.
Authors
Kaiming Xu, Ankita Bhardwaj, Sunil Koundal, Qin Ren, Chenyu You, Xenophon Papademetris, Helene Benveniste, Tryphon T. Georgiou
