Real-time monitoring of gadolinium diethylenetriamine penta-acetic acid during osmotic blood-brain barrier disruption using magnetic resonance imaging in normal wistar rats.

ABSTRACT

OBJECTIVE: Treatment of malignant gliomas is hampered by several factors, one of which is the blood-brain barrier (BBB). Thus, innovative strategies to cross the BBB have been developed, such as the BBB disruption procedure. Although it has been studied extensively, details regarding the physiology of the procedure remain obscure. This study was undertaken to clarify these issues. METHODS: Forty Wistar rats were imaged with a 7T animal magnetic resonance imaging scanner in dynamic acquisitions during BBB disruption. Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) was injected to visualize and characterize the permeability of the BBB at different time points after disruption. The concentration of Gd-DTPA in the brain parenchyma was determined as a function of time after injection. RESULTS: A typical pattern of signal change as a function of time was observed in the treated hemisphere of all animals. Initially, a slight signal decrease was observed in T1-weighted images followed by a strong increase corresponding to the injection of Gd-DTPA. Two different mechanisms seemed responsible for the distribution of Gd-DTPA within the parenchyma 1) a direct diffuse increase in capillary permeability, and 2) a diffusion process in the interstitial compartment. Initial results showed that the barrier opens immediately after the procedure and for at least 30 minutes. CONCLUSION: The methodology described in this article allows monitoring of the dynamics of the BBB disruption process and characterization of its physiology in vivo, and represents a marked advantage over postmortem static studies.