Development of an operator independent ultrasound therapeutic device for stroke treatment

Ischemic stroke is one of the leading causes of mortality and morbidity worldwide. Low intensity transcranially applied ultrasound has been shown to augment cerebral arterial recanalization when administered in conjunction with tPA. However, ultrasound usually requires an experienced operator for proper alignment and operation. We have developed an operator independent ("hands free") device that can deliver ultrasound therapy to a larger patient population by obviating the need for ultrasound specialists in emergency situations. Design goals thus included simple operation and high likelihood of successful insonation of blocked arteries. Ultrasound dosimetry and controlled insonation were also important design factors. Methods: The ultrasound delivery system includes a multiple transducer transcranial head frame comprising broadband (1.0 to 2.5 MHz) transducers placed at the temporal windows (six on each side) and the suboccipital window (six additional transducers). A computer controlled ultrasound generator-receiver system could energize any transducer with sine bursts of varying frequency, amplitude, duty factor and PRF. The system was controlled via USB to a laptop computer; a LabView program was used for the user interface, system control, and file management. Prior to use, ultrasonic dosimetry data was recorded for each transducer and saved in the system. The transmission characteristics could thus emulate the characteristics and dose levels of commercially available TCD systems and never exceed FDA ultrasound exposure limits. With the headframe on the patient, the system automatically determined which transducer was positioned over the thinnest temporal bone (the “temporal window”). This was done by sequentially firing each lateral transducer while the transducers on the opposite side of the skull were used as receivers. The transmitter/receiver combination which generated the highest signal (the “best pair”) was used for subsequent insonation. Results/Discussion: A safety trial was conducted using 15 healthy volunteers (with informed consent under IRB approval). In all test subjects, the “best pair” approach always found a temporal window location with adequate transmission properties. The mean estimated in vivo peak negative pressure at 3.2 cm intracranial depth was 59±17 kPa, and the maximum derated intensity (Ispta
₃
) levels did not exceed the 720 mW/cm
²
limit. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure and at 24 hrs (all NIHSS scores 0), and no breach of the Blood Brain Barrier was found on all MRI's repeated within 1 hour of the exposure. The system logged all exposures in real time for later analysis. The system is now in clinical test with stroke patients.