Simulation-based drug treatment planning

Patent metadata

Field	Value
Publication number	US-11857807-B2
Application number	US-201816622050-A
Country	US
Kind code	B2
Filing date	Jun 29, 2018
Priority date	Jun 29, 2017
Publication date	Jan 2, 2024
Grant date	Jan 2, 2024

Abstract

Various approaches for computationally generating a protocol for treatment of one or more target BBB regions within a tissue region of interest using a source of focused ultrasound include specifying (i) settings of sonication parameters for applying one or more sequence of sonications to the target BBB region using the source of focused ultrasound and (ii) a characteristic of microbubbles selected to be administered into the target BBB region; electronically simulating treatment in accordance with the protocol at least in part by computationally executing the sequence(s) of sonications and computationally administering the microbubbles having the characteristic; and computationally predicting a tissue disruption effect of the target BBB region resulting from the treatment.

First claim

What is claimed is:

1. A system for treating a target blood-brain barrier (BBB) region within a tissue region of interest, the system comprising:
an ultrasound transducer;
a processor; and
memory storing (i) a sonication parameter for applying at least one sequence of sonications to the target BBB region using the ultrasound transducer, (ii) a microbubble characteristic for microbubbles selected to be administered into the target BBB region, and (iii) instructions which, when executed by the processor, cause the processor to:
(a) electronically simulate treatment in accordance with the sonication parameter and the microbubble characteristic at least in part by computationally executing the at least one sequence of sonications and computationally administering the microbubbles having the microbubble characteristic;
(b) computationally predict a degree of tissue disruption of the target BBB region resulting from the treatment based on the simulation thereof;
(c) computationally generate a treatment protocol specifying the sonication parameter and the microbubble characteristic based at least in part on the predicted degree of tissue disruption; and
(d) activate the ultrasound transducer in accordance with the treatment protocol.

2. The system of claim 1 , wherein the processor is further configured to predict the degree of tissue disruption as a function of time.

3. The system of claim 1 , wherein the sonication parameter comprises an amplitude, a frequency, a beam shape, a phase, or a direction of at least one sonication in the at least one sequence of sonications.

4. The system of claim 1 , wherein the processor is further configured to:
(e) compare the predicted degree of tissue disruption against a target objective; and
(f) if the predicted degree of tissue disruption deviates from the target objective, alter the treatment protocol and repeat (a) through (d) for the altered treatment protocol, wherein altering the treatment protocol includes altering the microbubble characteristic.

5. The system of claim 4 , wherein the target objective comprises at least one of opening of the target BBB region, a target perfusion rate at the target BBB region, a target tissue permeability at the target BBB region, a safety threshold associated with the target BBB region or a safety threshold associated with tissue outside the target BBB region.

6. The system of claim 1 , wherein the treatment protocol specifies a plurality of sequences of sonications, and the processor is further configured to:
(e) compare the predicted degree of tissue disruption against a target objective; and
(f) if the predicted degree of tissue disruption deviates from the target objective, alter the microbubble characteristic in a subsequent sequence of sonications.

7. The system of claim 1 , wherein the treatment protocol specifies a plurality of sequences of sonications and the sonication parameter is a time interval between consecutive sonication sequences.

8. The system of claim 1 , wherein the processor is further configured to obtain a digital image of at least a portion of the target BBB region, and computationally identify a set of 3D voxels corresponding to the portion of the target BBB region and generate the treatment protocol based on the identified 3D voxels.

9. The system of claim 8 , wherein a plurality of target BBB regions are identified in the image and the treatment protocol specifies a plurality of sonication sequences each corresponding to one of the plurality of target BBB regions.

10. The system of claim 9 , wherein the processor is further configured to substantially simultaneously computationally apply the plurality of sonication sequences to the plurality of target BBB regions.

11. The system of claim 9 , wherein the processor is further configured to sequentially computationally apply the plurality of sonication sequences to the plurality of target BBB regions in round-robin fashion.

12. The system of claim 11 , wherein the processor is further configured to computationally predict microbubble cavitation resulting from the computationally executed sonications, and predict the degree of tissue disruption of the plurality of target BBB regions based at least in part on the predicted microbubble cavitation.

13. The system of claim 12 , wherein the processor is further configured to determine a sonication parameter associated with a second sonication sequence applied to a second target BBB region based at least in part on at least one of (i) the predicted microbubble cavitation or (ii) the degree of tissue disruption resulting from a first sonication sequence previously applied to a first target BBB region.

14. The system of claim 8 , wherein the processor is further configured to identify a plurality of tissue types in the target BBB region of the image, wherein the treatment protocol specifies a plurality of sonication sequences each corresponding to one of the identified tissue types.

15. The system of claim 1 , wherein the processor is further configured to predict the degree of tissue disruption based on retrospective administrations of magnetic resonance imaging (MRI) contrast agent into target BBB regions of a plurality of patients and diffusion thereof.

16. The system of claim 1 , wherein the microbubble characteristic specifies at least one of an agent type, a size, a concentration, a dose, an administration rate or timing, or a location of an injection site.

17. The system of claim 1 , further comprising a detection system, wherein the processor is further configured to:
(e) cause the detection system to monitor an actual treatment effect resulting from activation of the ultrasound transducer;
(f) compare the actual treatment effect with the computationally predicted degree of tissue disruption; and
(g) upon detection of a discrepancy between the actual treatment effect and the predicted degree of tissue disruption, adjust at least one of the sonication parameter or the microbubble characteristic in the treatment protocol.

18. The system of claim 1 , wherein the processor is further configured to cause a therapeutic agent to be administered into the target BBB region.

19. The system of claim 18 , wherein the therapeutic agent comprises at least one of Busulfan, Thiotepa, Lomustine, Carmustine, 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/ara-U.

20. The system of claim 1 , wherein the processor is further configured to cause a radiation dose to be applied to the tissue region.

Assignees

• Levy Yoav
• De Picciotto Rafi
• Grinfeld Javier
• Zadicario Eyal
• Insightec Ltd

Inventors

• Levy Yoav
• De Picciotto Rafi
• Grinfeld Javier
• Zadicario Eyal

Classifications

• A61N5/1049 Primary

  for verifying the position of the patient with respect to the radiation beam · CPC title

• A61B5/489

  Blood vessels · CPC title

• A61B34/10

  Computer-aided planning, simulation or modelling of surgical operations · CPC title

• A61M37/0092

  using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis · CPC title

• A61N5/103 Primary

  Treatment planning systems · CPC title