Methods and systems for selectively disrupting tissue with high intensity focused ultrasound

Abstract

Methods and systems for selectively disrupting tissue using high intensity focused ultrasound (“HIFU”) therapy are disclosed herein. A method of treating tissue in accordance with an embodiment of the present technology can include, for example, pulsing HIFU waves from an ultrasound source toward a volume of tissue that includes an extracellular matrix (“ECM”) and generating, from nonlinear propagation of the HIFU waves, shock waves in the tissue to induce boiling in the volume of the tissue. The method can further include lysing cells in the volume of tissue while leaving the ECM at least substantially intact. The emulsification of cells can be to a sufficient degree to decellularize the tissue and form a decellularized scaffold for subsequent tissue growth.

1 . A method of treating tissue, the method comprising:
 pulsing high intensity focused ultrasound (HIFU) waves from an ultrasound source toward a volume of tissue that includes an extracellular matrix (ECM);   generating, from nonlinear propagation of the HIFU waves, shock waves in the tissue to induce boiling in the volume of the tissue at a focus of the ultrasound source; and   lysing cells in the volume of tissue, via the HIFU waves, while leaving the ECM at least substantially intact.   
     
     
         2 . The method of  claim 1  wherein the focus of the ultrasound source is positioned a depth within the tissue, and wherein generating shock waves in the tissue includes generating shock waves having a peak positive pressure at the focus of at least 50 MPa. 
     
     
         3 . The method of  claim 1  wherein pulsing HIFU waves comprises pulsing HIFU waves such that each pulse has a duration of 0.1-100 ms. 
     
     
         4 . The method of  claim 1  wherein pulsing the HIFU waves further comprises pulsing the HIFU waves at a duty cycle of at most 5%. 
     
     
         5 . The method of  claim 1  wherein:
 the ultrasound source has a power of 250-5,000 W; 
 pulsing the HIFU waves further comprises pulsing the HIFU waves at a duty cycle of at most 5%, wherein individual pulses have a pulse length of 1-10 ms; 
 generating shock waves further comprises generating shock waves having a peak positive pressure of 50-150 MPa; and 
 lysing cells in the volume of tissue comprises preserving vessels in the volume of tissue having diameters of less than 50 μm. 
 
     
     
         6 . The method of  claim 1  wherein lysing cells in the volume of tissue further comprises at least substantially decellularizing the tissue to create a scaffold for subsequent cell regrowth. 
     
     
         7 . The method of  claim 1  wherein the volume of tissue is part of an ex vivo organ, and wherein:
 lysing cells in the volume of tissue further comprises at least substantially decellularizing the volume of tissue; and 
 the method further comprises moving a focus of the ultrasound source across the organ while pulsing HIFU waves and lysing cells to create a decellularized scaffold of the ex vivo organ. 
 
     
     
         8 . The method of  claim 7 , further comprising disposing cells on the decellularized scaffold to re-grow the organ. 
     
     
         9 . The method of  claim 1  wherein the volume of tissue is part of an in vivo tissue mass, and wherein:
 lysing cells in the volume of tissue further comprises at least substantially decellularizing the tissue; and 
 moving a focal region of the ultrasound source across the tissue mass while pulsing HIFU waves and lysing cells to create a decellularized scaffold. 
 
     
     
         10 . The method of  claim 1  wherein emulsifying the cells in the volume of tissue while leaving the ECM at least substantially intact further comprises forming a lesion in the tissue having a volume of at least 1 cm 3 . 
     
     
         11 . The method of  claim 1  wherein the shock waves in the tissue are distinct from shock waves resulting from cavitation. 
     
     
         12 . A method of treating tissue, the method comprising:
 applying, via an ultrasound source, high intensity focused ultrasound (HIFU) energy to a target site in tissue in accordance with a pulsing protocol, wherein—
 the individual pulses have a length of 0.1-100 ms, 
 the HIFU energy generates shock waves proximate to the target site in the tissue to induce boiling of the tissue at the target site, and 
 the target site is proximate to a focal region of the ultrasound source; and 
   forming a lesion in the tissue with the HIFU energy while preserving an extracellular matrix (ECM) in the lesion.   
     
     
         13 . The method of  claim 12  wherein forming the lesion in the tissue comprises at least decellularizing the tissue such that the ECM within the lesion is at least substantially free of cells. 
     
     
         14 . The method of  claim 12  wherein applying HIFU energy to the target site comprises:
 pulsing HIFU waves at a duty cycle of at most 5%; and 
 generating shock waves having a peak positive pressure of 50-150 MPa. 
 
     
     
         15 . A method of forming decellularized scaffolds, the method comprising:
 pulsing high intensity focused ultrasound (HIFU) energy from an ultrasound source toward a volume of tissue, wherein the volume of tissue includes an extracellular matrix (ECM); and   lysing cells of the tissue with the HIFU energy to at least partially decellularize the volume of tissue while leaving the ECM at least substantially intact to form a decellularized scaffold for subsequent tissue growth.   
     
     
         16 . The method of  claim 15  wherein pulsing HIFU energy toward the volume of tissue comprises generating, from nonlinear propagation of HIFU waves, shock waves in the tissue to induce boiling in the tissue. 
     
     
         17 . The method of  claim 15  wherein pulsing HIFU energy toward the volume of tissue comprises applying cavitation histotripsy to form a lesion in the volume of tissue. 
     
     
         18 . The method of  claim 15 , further comprising moving a focal region of the ultrasound source across portions of the tissue while pulsing the HIFU energy and lysing cells to form a lesion in the tissue having a volume of at least 1 cm 3 . 
     
     
         19 . The method of  claim 15  wherein the tissue is part of an ex vivo organ of a human body, and wherein emulsifying cells comprises decellularizing the ex vivo organ. 
     
     
         20 . The method of  claim 19 , further comprising disposing cells on the decellularized scaffold to re-grow the organ. 
     
     
         21 . The method of  claim 15 , further comprising perfusing vessels of the tissue with a decellularization detergent to further decellularize the tissue. 
     
     
         22 . The method of  claim 21  wherein perfusing vessels of the tissue with a decellularization agent occurs while the HIFU energy is applied to the tissue. 
     
     
         23 . The method of  claim 15  wherein the tissue is part of an in vivo organ of a human body, and wherein emulsifying cells comprises decellularizing at least a portion of the in vivo organ. 
     
     
         24 . The method of  claim 15  wherein pulsing HIFU energy further comprises applying HIFU energy to the volume of tissue in accordance with a pulsing protocol having a duty cycle of less than 5% and a pulse duration of at most 100 ms. 
     
     
         25 - 31 . (canceled)