Systems and methods for evaluating tissue of a subject

Abstract

The present disclosure is directed to relates to systems and methods for evaluating tissue using high intensity focused ultrasound (HIFU) energy. In one embodiment, for example, a system for treating a patient comprises an ultrasound source configured to deliver HIFU energy to a target tissue mass of the patient and a function generator operably coupled to the ultrasound source for initiating a pulsing protocol for delivering the HIFU energy. The system further comprises a controller configured to perform operations comprising applying HIFU energy to induce cavitation in the target tissue mass and cause a biomarker to be released, comparing a baseline concentration of the biomarker from a first fluid sample to a concentration of the biomarker in a second fluid sample within 2 hours after applying HIFU, and repeating the applying and comparing until the concentration of the biomarker in the fluid sample falls below a threshold value.

I/We claim: 
     
         1 . A system for treating a human patient, the system comprising:
 an ultrasound source configured to deliver high intensity focused ultrasound energy to a target tissue mass of the patient;   a function generator operably coupled to the ultrasound source, wherein the function generator initiates a pulsing protocol for delivering the high intensity focused ultrasound energy from the ultrasound source to the target tissue mass; and   a controller in communication with the ultrasound source and the function generator,   wherein controller is configured to perform operations comprising—   applying high intensity focused ultrasound energy to induce cavitation in the target tissue mass and cause a biomarker to be released from within the cells;   comparing (a) a baseline concentration of the biomarker from a first fluid sample of the patient to (b) a concentration of the biomarker in a second fluid sample of the subject within 2 hours after applying high intensity focused ultrasound energy to the target tissue mass; and   repeating the applying and comparing until the concentration of the biomarker in the fluid sample falls below a threshold value.   
     
     
         2 . The system of  claim 1  wherein a period of time between applying high intensity focused ultrasound energy and comparing a baseline concentration of the biomarker in the first fluid sample to the concentration of the biomarker in the second fluid sample is no more than about 1 hour. 
     
     
         3 . The system of  claim 1  wherein a period of time between applying high intensity focused ultrasound energy and comparing a baseline concentration of the biomarker in the first fluid sample to the concentration of the biomarker in the second fluid sample is no more than about 20 minutes. 
     
     
         4 . The system of  claim 1  wherein applying high intensity focused ultrasound energy to induce cavitation in the target tissue mass comprises inducing cavitation bubbles that reversibly permeabilize the cells. 
     
     
         5 . The system of  claim 1  wherein the function generator is configured to initiate the pulsing protocol for inducing shock waves having a pulse-average intensity of 25 kW/cm2 or greater. 
     
     
         6 . The system of  claim 1  wherein the function generator is configured to initiate the pulsing protocol for inducing shock waves having a pulse-average intensity of 40 kW/cm2 or greater. 
     
     
         7 . The system of  claim 1  wherein applying high intensity focused ultrasound energy to induce cavitation in the target tissue mass comprises inducing cavitation bubbles that reversibly permeabilize the cells. 
     
     
         8 . The system of  claim 1  wherein the threshold value of the biomarker is greater than the baseline concentration of the biomarker in the fluid before applying the high intensity focused ultrasound energy, and wherein the threshold value is at least 2 times greater than the baseline concentration. 
     
     
         9 . The system of  claim 1  wherein the biomarker comprises any one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6. 
     
     
         10 . The system of  claim 1  wherein the biomarker is released into a fluid of the patient, and wherein the fluid is selected from the group consisting of blood, a blood fraction, a blood derivative, a fluid fraction of blood, a non-fluid fraction of blood, whole blood, blood cells, microvesicles, cryoprecipitate, plasma, serum, subcellular vesicles, lymph fluid, ascites, urine, cerebrospinal fluid, seminal fluid, breast milk, breast secretions, breast aspirates, and feces. 
     
     
         11 . The system of  claim 1  wherein the fluid is blood, a blood fraction, or a blood derivative. 
     
     
         12 . A system for diagnosing a disease or an increased risk of a disease in a subject, the system comprising:
 an ultrasound source configured to non-invasively deliver high intensity focused ultrasound energy to a target tissue mass of the patient to cause release of a marker from the mass; and   a controller configured to determine a concentration of the marker in a fluid of the subject.   
     
     
         13 . The system of  claim 12  wherein the ultrasound source is configured to deliver sufficient high intensity focused ultrasound energy to the target tissue mass of the subject to induce cavitation bubble activity in the target tissue mass. 
     
     
         14 . The system of  claim 12  wherein the ultrasound source is configured to deliver sufficient high intensity focused ultrasound energy to the target tissue mass of the subject to induce boiling histotripsy in the target tissue mass. 
     
     
         15 . The system of  claim 12  wherein the disease is a cancer, and wherein the marker is a DNA, a RNA, a protein, or a small molecule. 
     
     
         16 . A method, comprising:
 determining a baseline concentration of a biomarker in a first fluid sample of a subject;   applying high intensity focused ultrasound nonlinear waveform energy to induce cavitation in a target tissue mass of the subject and cause the biomarker to be released from within cells of the target tissue mass;   determining a second concentration of the biomarker in a second fluid sample of the subject within 2 hours after applying high intensity focused ultrasound nonlinear waveform energy to the target tissue mass; and   repeating the applying and determining until the second concentration of the biomarker in the fluid sample falls below a threshold value.   
     
     
         17 . The method of  claim 16  wherein the target tissue mass is a tumor and the biomarker is a miRNA. 
     
     
         18 . The method of  claim 16  wherein the amount of the biomarker released from within the cells of the target tissue mass is determined by determining a concentration of the biomarker in a fluid of the subject, wherein the fluid is selected from the group consisting of blood, a blood fraction, a blood derivative, a fluid fraction of blood, a non-fluid fraction of blood, whole blood, blood cells, microvesicles, cryoprecipitate, plasma, serum, subcellular vesicles, lymph fluid, ascites, urine, cerebrospinal fluid, seminal fluid, breast milk, breast secretions, breast aspirates, and feces. 
     
     
         19 . The method of  claim 16  wherein the threshold value of the biomarker is greater than the baseline concentration of the biomarker in the first fluid sample before applying the high intensity focused ultrasound nonlinear waveform energy, and wherein the threshold value is at least 2 times greater than the baseline concentration. 
     
     
         20 . The method of  claim 16  wherein a period of time between applying high intensity focused ultrasound nonlinear waveform energy to the target tissue mass and determining the second concentration of the biomarker is no more than 20 minutes.