Non-contrast MR imaging of blood-brain barrier permeability to water

Purpose: Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water. Methods: The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction (E) and permeability-surface-area product (PS) of BBB can be determined. Four studies were performed. We first demonstrated the proof-of-principle using conventional ASL with very long post-labeling delays (PLD). Next, a new sequence, dubbed water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), and its Look-Locker (LL) version were developed. Finally, we demonstrated that the sensitivity of the technique can be significantly enhanced by acquiring the data under mild hypercapnia. Results: By combining a strong background suppression with long PLDs (2500–4500 ms), ASL spins were reliably detected in the superior sagittal sinus (SSS), demonstrating the feasibility of measuring this signal. The WEPCAST sequence eliminated partial voluming effects of tissue perfusion and allowed quantitative estimation of E = 95.5 ± 1.1% and PS = 188.9 ± 13.4 mL/100 g/min, which were in good agreement with literature reports. LL-WEPCAST sequence shortened the scan time from 19 min to 5 min while providing results consistent with multiple single-PLD acquisitions. Mild hypercapnia increased SNR by 78 ± 25% without causing a discomfort in participants. Conclusion: A new non-contrast technique for the assessment of global BBB permeability was developed, which may have important clinical applications.