Low intensity ultrasound therapy
Provided herein methods for treating a subject suffering from a disease or a disorder associated with hyperproliferating cells, by irradiating the cells with low-frequency ultrasound at an intensity that is either below the cavitational threshold intensity for the ultrasound frequency, or is characterized by a low-frequency mechanical index below 2.5. The methods may further comprise determining an elasticity value of the cells, and adjusting the ultrasound intensity accordingly.
1. A method of treating a subject suffering from a disease or a disorder associated with hyperproliferating cells, said method comprising non-invasively irradiating a tissue comprising said hyperproliferating cells in said subject with ultrasound, said ultrasound having a frequency between 20 and 200 kHz, at an intensity between 0.5 and 100 W/cm 2 , provided that the intensity is characterized by a low-frequency mechanical index of between 1 and 2.5, wherein said intensity produces a mechanical index lower than 2.5, and wherein said method comprises evaluating a mechanical stiffness of said hyperproliferating cells, prior to said irradiating, and adjusting said intensity based on said evaluating.
2. The method according to claim 1 , wherein said evaluating comprises obtaining a ratio between elasticity values of said hyperproliferating cells and healthy tissue cells obtained from a vicinity of said hyperproliferating cells.
3. The method according to claim 2 , wherein said elasticity values are obtained by determining Young's modulus of said hyperproliferating cells in a sample obtained from said subject.
4. The method according to claim 2 , wherein said elasticity value of said healthy tissue cells is determined based on reference values of Young's modulus characteristic of said healthy tissue cells.
5. The method according to claim 1 , wherein said evaluating is performed by atomic force microscopy.
6. The method according to claim 1 , wherein said evaluating is performed by confocal microscopy with F-actin staining.
7. The method according to claim 1 , wherein said adjusting of the intensity comprises determining a maximal intensity producing a mechanical index of 2.5, and administering the ultrasound at an intensity of between 1 and 40% of the maximum intensity if a ratio of elasticity values is between 0.01 and 0.15, administering ultrasound at an intensity of between 10 and 80% of the maximum intensity if the ratio of elasticity values is between 0.15 and 0.35, and administering ultrasound at an intensity of between 25 and 100% of the maximum intensity if the ratio of elasticity values is between 0.35 and 0.7.