Focused ultrasound (FUS) and microbubbles can open the blood-spinal cord barrier (BSCB) and enhance therapeutic delivery. Short-burst phase keying (SBPK) exposures (pulse-train of closely timed short bursts) have been developed to address clinical-scale, spine specific targeting challenges in a dual-aperture configuration, and have led to successful BSCB opening (BSCBO) in animal models. Here we study the effect of varying sonication parameters in vivo. The effect of varying acoustic pressure (P, n = 4), burst length (BL, n = 3), burst repetition frequency (BRF, n = 4), pulse-train length(PL, n = 4), and total treatment duration (τ, n = 4), compared with a control sonication (P = 0.28 MPa, BL = 2 cycles, BRF = 20 kHz, PL = 10 ms, τ = 120 s, frequency = 514 kHz, PRF = 1 Hz), was investigated in Sprague Dawley rats (3-4 locations/spinal cord). BSCBO was assessed using T1-weighted contrast-enhanced MRI. Statistical significance was assessed using a paired t-test (p < 0.05). Increased P led to increased MRI enhancement (0.23 MPa: 17.8 ± 4.9%, 0.28 MPa: 25.9 ± 8.0%, 0.33 MPa: 33.9 ± 8.8%). τ = 300 s showed increased enhancement compared with the control (29.5 ± 8.7 vs 22.2 ± 2.8%, p = 0.03), while BL = 5 showed a trend towards increasing enhancement, although without significance (36.6 ± 7.2% vs. 31.2 ± 3.0%, p = 0.17). Varying PL or BRF did not impact mean enhancement. Preliminary results show that increasing treatment duration improves the efficacy of SBPK FUS-induced BSCBO and increasing burst length may have some benefit. Future work will include histological assessment of tissue damage.