CONTROLLING DELIVERY OF THERAPEUTIC AGENT IN MICROBUBBLE-ENHANCED ULTRASOUND PROCEDURES
Various approaches for microbubble-enhanced ultrasound treatment of target tissue include receiving a desired characteristic of the microbubbles for treating the target tissue; causing the microbubbles to be dispensed from the administration device; and comparing a characteristic of the dispensed microbubbles to the desired characteristic so as to validate a match therebetween.
1 . A system for microbubble-enhanced treatment of target tissue, the system comprising:
an administration device comprising a first storage container for storing microbubbles; and
a controller configured to:
(a) receive a desired characteristic of the microbubbles for treating the target tissue;
(b) cause the microbubbles to be dispensed from the administration device; and
(c) compare a characteristic of the dispensed microbubbles to the desired characteristic so as to validate a match therebetween.
2 . The system of claim 1 , wherein the controller is further configured to cause the dispensed microbubbles to be introduced to the target tissue upon validation of the match.
3 . The system of claim 1 , wherein the controller is further configured to cause a precautionary action upon detecting a clinically significant deviation between the characteristic of the dispensed microbubbles from the desired characteristic.
4 . The system of claim 1 , further comprising a measurement system for measuring the characteristic of the dispensed microbubbles.
5 . The system of claim 4 , wherein the measurement system comprises an acoustic system.
6 . The system of claim 5 , wherein the acoustic system is configured to apply a plurality of frequencies to the microbubbles for measuring the characteristic thereof
7 . The system of claim 5 , wherein the acoustic system is configured to measure at least one of attenuation, scattering, backscattering, harmonic generation, or sub-harmonic generation from the microbubbles.
8 . The system of claim 4 , wherein the measurement system is configured to perform measurements of at least one of a laser light obscuration and scattering, electrozone sensing, optical microscopy or flow cytometry.
9 . The system of claim 4 , wherein the measurement system comprises at least one sensor for measuring an administration rate of the microbubbles.
10 . The system of claim 4 , further comprising an ultrasound transducer for transmitting ultrasound waves to the microbubbles, wherein the measurement system is configured to monitor a response of the microbubbles to the ultrasound waves.
11 . The system of claim 10 , wherein the controller is further configured to adjust at least one of an ultrasound parameter or the characteristic of the dispensed microbubbles based at least in part on the monitored response thereof.
12 . The system of claim 11 , wherein the ultrasound parameter comprises at least one of a frequency, a phase, or an amplitude of a signal driving the ultrasound transducer.
13 . The system of claim 1 , further comprising an ultrasound transducer, wherein the administration device further comprises a second storage container for storing a therapeutic agent and the controller is further configured to:
cause the ultrasound transducer to transmit treatment ultrasound waves to the target tissue and generate an acoustic field therein; and
cause administration of the therapeutic agent so as to produce an optimal treatment effect in the target tissue.
14 . The system of claim 13 , further comprising a measurement system for detecting signals indicating a condition of a treatment procedure.
15 . The system of claim 14 , wherein the condition of the treatment procedure comprises at least one of a condition of the target tissue, a condition of the therapeutic agent, or a condition of the microbubbles.
16 . The system of claim 15 , wherein the condition of the microbubbles is a cavitation state thereof.
17 . The system of claim 15 , wherein the condition of the target tissue comprises at least one of a temperature, a size, a shape or a location of the target tissue.
18 . The system of claim 14 , wherein the measurement system comprises at least one of an imager or an acoustic-signal detector.
19 . The system of claim 14 , wherein the controller is further configured to adjust the characteristic of at least one of the administered microbubbles or the administered therapeutic agent based at least in part on the detected signals.
20 . The system of claim 19 , wherein the characteristic is at least one of an agent type, a size, a concentration, an administering rate, an administering dose, an administering pattern, an administering time or an administering pressure of the administered microbubbles and/or therapeutic agent.
21 . The system of claim 13 , wherein the controller is further configured to cause the ultrasound transducer to transmit ultrasound waves to the target tissue in the presence of the administered microbubbles.
22 . The system of claim 13 , wherein the administration device further comprises a third storage container for storing a contrast agent.
23 . The system of claim 22 , wherein the administration device further comprises:
an actuation mechanism;
an introducing device for delivering at least one of the microbubbles, therapeutic agent, or contrast agent to the target tissue; and
at least one channel for delivering at least one of the microbubbles, contrast agent or therapeutic agent from the corresponding storage container to the introducing device.
24 . The system of claim 13 , wherein the therapeutic agent comprises at least one of Busulfan, Thiotepa, CCNU (lomustine), BCNU (carmustine), ACNU (nimustine), Temozolomide, Methotrexate, Topotecan, Cisplatin, Etoposide, Irinotecan/SN-38, Carboplatin, Doxorubicin, Vinblastine, Vincristine, Procarbazine, Paclitaxel, Fotemustine, Ifosfamide/4-Hydroxyifosfamide/aldoifosfamide, Bevacizumab, 5-Fluorouracil, Bleomycin, Hydroxyurea, Docetaxel, or Cytarabine (cytosine arabinoside, ara-C)/ara-U.
25 . The system of claim 1 , wherein the first storage container is connected to a plurality of channels, each having a manipulation means for changing the microbubble characteristic.
26 . The system of claim 25 , wherein the manipulation means comprises a plurality of filters having different exclusion sizes, the controller being configured to:
select a channel having one of the filters corresponding to the desired microbubble characteristic; and
cause the microbubbles to be administered only through the selected channel.
27 . The system of claim 25 , wherein the manipulation means comprises applying an acoustic field to the microbubbles.
28 . The system of claim 27 , wherein the controller is further configured to tune a frequency band of the acoustic field so as to destroy the microbubbles having a size outside a desired size range.
29 . The system of claim 1 , further comprising a plurality of storage containers, each containing microbubbles having a different size characteristic, the controller being configured to:
select one of the storage containers having therein microbubbles corresponding to the desired microbubble characteristic; and
cause the microbubbles to be administered only from the selected storage container.
30 . The system of claim 1 , further comprising a radiation device for transmitting a radiation dose to the target tissue.
31 . The system of claim 1 , wherein the controller is further configured to dispense the microbubbles from the administration device based at least in part on a predetermined administration profile.
32 . The system of claim 31 , wherein the administration profile is determined based at least in part on the characteristic of the dispensed microbubbles.
33 . The system of claim 32 , wherein the characteristic of the dispensed microbubbles comprises at least one of a diameter, a size distribution, a shell composition, a gas composition or a liquid core composition.
34 . The system of claim 31 , wherein the administration profile comprises at least one of a dose, a concentration, an administering rate, an administering timing or an administering pressure of the microbubbles.
35 . The system of claim 1 , further comprising a preparation device for preparing the microbubbles based at least in part on the desired characteristic.
36 . The system of claim 1 , wherein the controller is further configured to acquire a characteristic of the target tissue and determine the desired characteristic of the microbubbles based at least in part on the characteristic of the target tissue.
37 - 90 . (canceled)