Targeted Lesion Generation Through the Skull Without Aberration Correction Using Histotripsy

Abstract

This study demonstrates the ability of histotripsy to generate targeted lesions through the skullcap without using aberration correction. Histotripsy therapy was delivered using a 500 kHz, 256-element hemispherical transducer with an aperture diameter of 30 cm and a focal distance of 15 cm fabricated in our lab. This transducer is theoretically capable of producing peak rarefactional pressures, based on linear estimation, (p-)LE, in the free field in excess of 200MPa with pulse durations 2 acoustic cycles. Three excised human skullcaps were used displaying attenuations of 73-81% of the acoustic pressure without aberration correction. Through all three skullcaps, compact lesions with radii less than 1mm were generated in red blood cell (RBC) agarose tissue phantoms without aberration correction, using estimated (p-)LE of 28-39MPa, a pulse repetition frequency of 1Hz, and a total number of 300 pulses. Lesion generation was consistently observed at the geometric focus of the transducer as the position of the skullcap with respect to the transducer was varied, and multiple patterned lesions were generated transcranially by mechanically adjusting the position of the skullcap with respect to the transducer to target different regions within. These results show that compact, targeted lesions with sharp boundaries can be generated through intact skullcaps using histotripsy with very short pulses without using aberration correction. Such capability has the potential to greatly simplify transcranial ultrasound therapy for non-invasive transcranial applications, as current ultrasound transcranial therapy techniques all require sophisticated aberration correction.

Fig. 1.

An image of the 500 kHz 256-element transducer used to deliver histotripsy treatments with a skullcap mounted within it. The bright spot seen in the center of the skullcap is the reflected laser light used for backlighting the images of the bubble clouds and lesions generated in the RBC phantoms (not shown).

Fig. 2.

Schematic drawing showing the alignment of the transducer’s focus within the skullcap.

Fig. 3.

Schematic of the experimental setup used for imaging experiments studying single lesion generation through the skullcap. A computer was used to send a trigger signal to the camera and laser for imaging purposes and to the FPGA boards to fire the high voltage pulser responsible for generating the ultrasound pulses used for treatment.

Fig. 4.

Direct measurements of the pressure waveforms at the transducer focus in the free field and through the three skullcaps using a fiber optic hydrophone.

Fig. 5.

Comparison plots of the pressure profiles measured through the skullcaps in comparison to the free field in the transverse (x) and axial (z) directions of the transducer.

Fig. 6.

Typical bubble clouds and lesions generated in RBC phantoms without aberration correction through the skullcaps used in experiments. The left column shows typical cavitation bubbles generated during treatment (the dark central regions) and the right column shows typical lesions (the bright central regions)

Fig. 7.

An image showing the grid of lesions generated through Skullcap 3 by mechanically repositioning the skullcap with respect to the transducer in 4 mm increments to generate a 1.6×1.6 cm square grid. The intesection points of the grid lines overlaying this image represent the fixed points onto which lesion generation was mechanically steered. These lesions were generated by applying histotripsy pulses through the skullcap without using aberration correction.

Fig. 8.

An image showing a patterned lesion in the shape of a 1 cm wide block ‘M’ generated through Skullcap 3 by mechanically repositioning the skullcap with respect to the transducer to generate the lesion. This lesion was generated by applying histotripsy pulses through the skullcap without using aberration correction.