Mechanical pulsed ultrasound therapy for modulating neural tissue microenvironments
Short ultrasound pulses or bursts, delivered at intermediate intensity to the target brain tissue transmits acoustic radiation forces into the targeted brain tissue without generating acoustic cavitation and without cellular fractionization. Thus, the present invention exploits the mechanical effects of high-intensity pressure fields only, without cavitation, by optimizing the interaction between acoustic pulses and radiation forces to apply a negative pressure to the brain tissue and degrading the perineuronal nets in the brain tissue and opening the blood-brain barrier.
1 . A method for controlled mechanical degradation of an extracellular matrix of brain tissue of a patient, the brain tissue having a cavitation threshold at which cavitation occurs, the method comprising:
outputting a treatment ultrasound pulse sequence directed at a treatment portion of the extracellular matrix of the brain wherein the treatment ultrasound pulse sequence is at a pulse intensity that is less than the cavitation threshold and at least partially degrades the extracellular matrix of the brain tissue in the treatment portion;
concurrent with the outputting of the treatment ultrasound pulse sequence, monitoring an amount of mechanical degradation of the extracellular matrix of the brain tissue in the treatment portion;
concurrent with the outputting of the treatment ultrasound pulse sequence, adjusting the treatment ultrasound pulse sequence based on the monitoring of the amount of mechanical degradation of the extracellular matrix of the brain tissue; and
wherein the ultrasound pulse sequence is comprised of pulses each having a length of less than or equal to 20 us and a duty cycle of less than or equal to 2%.
2 . The method of claim 1 wherein a peak negative pressure of the treatment ultrasound pulse sequence is less than or equal to 20 MPa.
3 . The method of claim 2 wherein a peak negative pressure of the treatment ultrasound pulse sequence is less than or equal to 15 MPa.
4 . The method of claim 1 wherein a peak positive pressure of the treatment ultrasound pulse sequence is less than or equal to 60 MPa.
5 . The method of claim 1 wherein a frequency of the treatment ultrasound pulse sequence is between 500 kHz and 1 MHz.
6 . The method of claim 1 wherein a pulse repetition frequency (PRF) of the treatment ultrasound pulse sequence is between 250 Hz and 750 Hz.
7 . The method of claim 1 wherein a duty cycle of the treatment ultrasound pulse sequence is less than or equal to 1%.
8 . The method of claim 1 wherein pulse length of the treatment ultrasound pulse sequence is less than or equal to 15 usec.
9 . The method of claim 1 wherein a number of pulses in the treatment ultrasound pulse sequence is 10 to 50 pulses.
10 . The method of claim 1 wherein an exposure duration of the treatment ultrasound pulse sequence is less than 60 sec.
11 . The method of claim 1 further including the steps of monitoring cavitation in the treatment portion; and
adjusting the energy of the ultrasound pulse sequence based on the monitoring of cavitation in the treatment portion.
12 . The method of claim 1 wherein the monitoring of the amount of degradation of the extracellular matrix of the brain tissue in the treatment region is performed using a monitoring ultrasound transducer.