BBB-Permeability Assessment via DCE-MRI

Upon completion of the FUS sonication, the mice were imaged in a 9.4 T MRI system (DRX400, Bruker Biospin, Billerica, MA, USA). Each mouse was inserted in a 30 mm diameter single resonator, while anesthetized orally with isoflurane (1–2%). Transverse images were acquired with a T₁-weighted 2D FLASH sequence of a 192 × 128 matrix size (reconstructed to 256 × 128), a resolution of 130 × 130 μm² (reconstructed to 98 × 130 μm²), a flip angle of 70°, TR/TE = 230/2.9 ms and a slice thickness of 0.6 mm without any interslice gap. The number of excitations (NEX) was equal to four and the acquisition time was 88 s. An intraperitoneal (IP) catheterization of the mouse allowed us to collect DCE-MR images before and after administration of 0.3 mL non-diluted gadodiamide (Omniscan®, GE Healthcare, Princeton, NJ, USA) without changing the initial position of the animal. The gadodiamide bolus was manually injected at a rate of approximately 10 μL s⁻¹. The relatively large dosage was preferred in order to secure the presence of a bolus peak in the vascular system, which is essential for the AIF determination, but also to allow DCE-MRI to obtain accurate tissue concentrations. Gadodiamide (Gd-DTPA) has been shown to reduce the longitudinal relaxation rate when it diffuses to the extravascular extracellular region, thus enhancing the T₁ signal intensity in the region, where the BBB opening has occurred. Gd-DTPA was injected approximately 30–60 min after sonication and the respiration of the mouse was monitored throughout the entire procedure. Forty sequential images were acquired over a time window of approximately 55 min after Gd-DTPA injection, which depicted the diffusion of the contrast agent into the targeted hippocampus and the surrounding area. Higher spatial resolution, transverse T₁- and T₂-weighted images were acquired after the DCE-MRI acquisition with 2D FLASH (TR/TE = 230/3.3 ms; flip angle: 70°; NEX = 18; scan time: 9 min 56 s; matrix size: 256 × 192; spatial resolution: 86 × 86 μm²; slice thickness: 500 μm, no interslice gap) and 2D RARE (TR/TE = 3300/43.8 ms; echo train: 8; NEX = 10; scan time: 9 min 54 s; matrix size: 256 × 192; spatial resolution: 86 × 86 μm²; slice thickness: 500 μm, no interslice gap) sequences, respectively.