Background Traumatic brain injury (TBI) and other acute intracranial pathologies disrupt the glymphatic system, a recently described waste-clearance network that facilitates the removal of metabolic byproducts from the brain. Dysfunction of this system after injury may contribute to impaired clearance of toxic metabolites, cerebral edema, and elevated intracranial pressure. This study aimed to evaluate glymphatic dynamics using intrathecal (IT) administration of gadoterate meglumine via an external ventricular drain (EVD) to better understand the impact of intracranial injury on glymphatic flow. Methods This single-center retrospective study, conducted from July 2025 to November 2025, enrolled six patients who were admitted for an intracranial pathology that required placement of an EVD to study the glymphatic system utilizing IT administration of contrast agent gadoterate meglumine. Serial magnetic resonance imaging (MRI) brain scans were performed pre-contrast and at least one additional time, either four, 12, or 36 hours after contrast administration. Intensity measurements were then taken on the images and compared at the following brain parenchymal locations: bilateral frontal white and grey matter, bilateral temporal white and grey matter, bilateral parietal white and grey matter, central pons located ventral to the cerebral aqueduct, central medulla located ventral to the fourth ventricle, and bilateral cerebellar white matter. Results No immediate procedural complications were observed following IT contrast administration. Patients demonstrated variable degrees of MRI signal change that correlated with presumed glymphatic function, with increased enhancement observed in regions of preserved flow and reduced enhancement in areas affected by intracranial pathology. In some cases, transient decreases in signal intensity were observed following contrast administration, which may reflect localized high-concentration contrast effects with susceptibility-related signal loss (“first-pass” phenomenon), altered glymphatic transport, or impaired clearance. Reduced glymphatic tracer propagation and diminished enhancement were observed in patients with neurological decline, whereas enhanced glymphatic transport was noted following EVD placement. One patient experienced neurological deterioration following IT contrast administration; however, given the presence of multiple confounding clinical factors, a causal relationship could not be established. Conclusions The glymphatic system plays a critical role in intracranial homeostasis and appears to be disrupted following acute brain injury. IT contrast-enhanced MRI enables visualization of glymphatic dynamics and demonstrates regional variation in tracer movement corresponding to underlying pathology. While low-dose IT gadolinium administration has demonstrated tolerability in prior human studies, the present findings highlight that definitive conclusions regarding safety and causality cannot be drawn from this small cohort. These results support the feasibility of IT contrast-enhanced MRI for evaluating glymphatic function, but larger prospective studies are needed to better define safety, pathophysiological mechanisms, and clinical implications.
Wong et al. (Tue,) studied this question.
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