Table 2.

Comparison of different commercial bubbles regarding BBB opening.

Ref	Bubble Type	Injection Dose (µL/kg)	Number of Bubbles per mL	Animal	Acoustic Parameters	Evans Blue Leakage	Damages Score
Bing et al. [38]	Optison	30	7 × 108	Sprague Dawley rats (230–300 g)	PnP = 0.47 MPa	High	NA
	Definity	6	1 × 1010		fc = 0.75 MHz	Moderate	NA
					PRF = 1 Hz
					duration = 120 s
					burst = 10 s
Shin et al. [36]	SonoVue	30	2 × 108	Sprague Dawley rats (250–300 g)	PnP = 0.3 MPa	4.45%	1
					fc = 0.5 MHz
	Definity	20	1 × 1010		PRF = 2 Hz	13.72%	0
	Definity	100	1 × 1010		duration = 60 s	16.35%	1
					burst = 10 s
Wu et al. [37]	SonoVue	200	2 × 108	Sprague Dawley rats (250–300 g)	PnP = 0.39 MPa	0.79 ± 0.24 µM	0
					fc = 0.4 MHz
					PRF = 1 Hz
	Definity	4	1 × 1010		duration = 120 s	0.52 ± 0.25 µM	0
					burst = 10 s
	USphere	1.43	2.8 × 1010			0.2 ± 0.04 µM	0
Omata et al. [68]	Sonazoid	3333	9 × 108	ddY mice (6 week old)	Intensity = 0.5 W/cm2	18 ± 7 µg/g brain	0
	SonoVue	30,000	1 × 108		fc = 3 MHz	5 ± 1 µg/g brain	0
					PRF = 10 Hz
					duration = 180 s
					burst = 50 s

PnP = Peak negative Pressure; fc = central frequency; PRF = Pulse repetition frequency; NA: non-assessed; the damage score grades hemorrhage and tissue damages: grade 0—normal tissue, grade 1—scattered or discontinuous erythrocyte extravasation, grade 2—continuous extravasation or microhemorrhage, grade 3—hemorrhage with necrotic damage or gross hemorrhage [27].