Figure 1:

MRI-guided sonobiopsy changed composition of circulating phosphorylated tau (p-tau) species in 2-month-old PS19 mice (experiment 1). (A) Diagram of the focused ultrasound (FUS) system in the small-animal MRI scanner. The mouse head was fixed in the MRI coil, and the focused ultrasound transducer was coupled to the skull with ultrasound gel and a water balloon filled with degassed water. (B) Schematic of the focused ultrasound trajectory targeting the right cerebral hemisphere. (C) T1-weighted MRI scans were acquired before focused ultrasound and intravenous contrast material administration. (D) Post-focused ultrasound/postcontrast T1-weighted MRI scans confirmed focused ultrasound–induced blood-brain barrier (BBB) disruption as a signal enhancement. Except for one wild-type mouse, successful BBB opening was observed in all mice that underwent focused ultrasound (six of seven wild-type mice, seven of seven PS19 mice). The wild-type mouse with no evidence of BBB opening after focused ultrasound was excluded from further analysis. There was no significant group difference (P = .71) in the volume of focused ultrasound–mediated BBB opening between PS19 (mean, 30.88 mm³ ± 17.94 [SD]) and wild-type (35.12 mm³ ± 22.94) mice. (E) In PS19 mice, normalized p-tau-181 (p-tau-181–to–m-tau ratio) was significantly greater (P = .006) in the sonobiopsy group (n = 7; mean, 0.57 ± 0.19) compared with the normalized pTau-181 in the blood-based liquid biopsy (blood LBx) group (ie, control group without focused ultrasound treatment; n = 8; mean, 0.36 ± 0.09). (F) In PS19 mice, the normalized pTau-231 (pTau-231–to–m-tau ratio) was significantly greater (P = .048) in the sonobiopsy group (n = 8; mean, 0.17 ± 0.06) compared with the normalized pTau-181 in the blood LBx group (n = 7; mean, 0.13 ± 0.03). Black bars indicate median in E and F.