Targeted delivery of active agents using thermally stimulated large increase of perfusion by high intensity focused ultrasound

A method for increasing the efficacy of a therapeutic agent in a target tissue, in a subject in need thereof, comprising:

• positioning a Magnetic Resonance guided high intensity focused ultrasound transducer to target the target tissue;
• energizing the Magnetic Resonance guided high intensity focused ultrasound transducer to thermally stimulate the target tissue;
• utilizing a Magnetic Resonance guided high intensity focused ultrasound system to monitor the spatial and temporal temperature distribution of the target tissue,
• wherein the monitoring comprises acquiring magnetic resonance thermometry images of the target tissue, and
• wherein the magnetic resonance thermometry images of the target tissue provide the spatial and temporal temperature distribution of the target tissue;
• extracting thermal conductivity as a function of temperature for controlled increase of blood perfusion from a measured spatial and temporal temperature distribution of the target tissue during and after thermal stimulation;
• extracting a temperature dependent perfusion rate from the spatial and temporal temperature distribution of the target tissue during and after thermal stimulation, wherein the extraction of temperature dependent perfusion rate is based, at least in part, on the thermal conductivity;
• administering a therapeutic agent to the subject;
• providing a controlled thermal stimulation to the target tissue,
• wherein the controlled thermal stimulation is provided by the Magnetic Resonance guided high intensity focused ultrasound transducer while monitoring the spatial and temporal temperature distribution of the target tissue,
• wherein the controlled thermal stimulation results in a temperature dependent control of blood perfusion rate to the target tissue, thereby resulting in a temperature dependent controlled increase of blood perfusion to the target tissue, and
• wherein the controlled increase of blood perfusion results in accumulation of the therapeutic agent in the target tissue;
• and
• discontinuing delivery of ultrasound energy when the monitored temperature of the target tissue achieves a pre-determined set temperature or temperature profile.