System and method for unbinding of plasma protein-bound active agents using an ultrasound system
An ultrasound system for use in unbinding an active agent from a plasma protein in a target site in a subject includes a transducer configured to generate acoustic pressure waves and a controller coupled to the transducer. The controller is programmed to control the transducer to produce a plurality of pulsed acoustic pressure waves in the target site of the patient. The plurality of pulsed acoustic pressure waves disrupt a plasma protein binding between the active agent and the plasma protein within the target site. The disruption of the plasma protein binding causes an increase in an amount of unbound active agent in the target site.
1 . An ultrasound system for use in unbinding an active agent from a plasma protein in a target site in a subject having 1) unbound active agent that is not bound to the plasma protein and 2) bound active agent comprising the active agent bound to the plasma protein, the ultrasound system comprising:
a transducer configured to generate acoustic pressure waves; and
a controller coupled to the transducer and programmed to control the transducer to produce a plurality of pulsed acoustic pressure waves in the target site of the subject the plurality of pulsed acoustic pressure waves having a set of parameters including an acoustic intensity configured to 1) disrupt a plasma protein binding between the active agent and the plasma protein of the bound active agent within the target site to cause an increase in an amount of unbound active agent in the target site, 2) ensure cavitation below a predetermined cavitation threshold, and 3) maintain a temperature of the target site below a predetermined temperature threshold.
2 . The ultrasound system according to claim 1 , wherein the controller is programmed to control the transducer to produce a focused plurality of pulsed acoustic pressure waves.
3 . The ultrasound system according to claim 1 , wherein the controller is programmed to control the transducer to produce an unfocused plurality of pulsed acoustic pressure waves.
4 . The ultrasound system according to claim 1 , wherein the set of parameters further includes at least one of a tone burst duration, a pulse repetition frequency, and a duty cycle.
5 . The ultrasound system according to claim 1 , wherein the acoustic intensity of the plurality of acoustic pressure waves is selected to produce a mechanical index (MI) below a predetermined MI threshold.
6 . The ultrasound system according to claim 1 , wherein the target site is a region of a brain.
7 . The ultrasound system according to claim 1 , wherein the plurality of pulsed acoustic pressure waves comprises one or more pulses having a tone burst duration in a range of 51 to 210 ms.
8 . The ultrasound system according to claim 1 , wherein the plurality of pulsed acoustic pressure waves comprises one or more pulses having a duty cycle in a range of 21% to 100%.
9 . The ultrasound system according to claim 6 , wherein the plurality of pulsed acoustic pressure waves comprises one or more pulses having a frequency between 100 kHz and 750 kHz.
10 . A method for unbinding an active agent from a plasma protein in a target site in a subject using an ultrasound system having a transducer and a controller, the target site having 1) unbound active agent that is not bound to the plasma protein and 2) bound active agent comprising the active agent bound to the plasma protein, the method comprising:
determining, using the controller, a set of parameters for a plurality of pulsed acoustic pressure waves including an acoustic intensity configured to 1) disrupt a plasma protein binding between the active agent and the plasma protein of the bound active agent within the target site to cause an increase in an amount of unbound active agent in the target site; 2) ensure cavitation below a predetermined cavitation threshold, and 3) maintain a temperature of the target site below a predetermined temperature threshold; and
generating, using the transducer, the plurality of pulsed acoustic pressure waves in the target site of the subject.
11 . The method according to claim 10 , wherein generating the plurality of pulsed acoustic pressure waves includes generating a focused plurality of pulsed acoustic pressure waves.
12 . The method according to claim 10 , wherein generating the plurality of pulsed acoustic pressure waves includes generating an unfocused plurality of pulsed acoustic pressure waves.
13 . The method according to claim 10 , wherein determining the set of parameters includes determining a frequency of the plurality of pulsed acoustic pressures waves in a range 100 kHz to 750 kHz based on the target site.
14 . The method according to claim 10 , wherein determining the set of parameters includes determining the acoustic intensity of the plurality of pulsed acoustic pressures waves to produce a mechanical index (MI) below a predetermined MI threshold.
15 . The method according to claim 14 , wherein determining the set of parameters includes selecting a tone burst duration for at least one pulse in the plurality of pulsed acoustic pressure waves from a range 51 to 210 ms.
16 . The method according to claim 15 , wherein determining the set of parameters includes selecting a duty cycle for at least one pulse in the plurality of pulsed acoustic pressure waves from a range 21% to 100%.
17 . The method according to claim 16 , wherein determining the set of parameters includes adjusting at least one of the parameters in the set of parameters until estimated or measured thermal effects are below a predetermined threshold.
18 . The method according to claim 10 , wherein the target site is a region of a brain.