Ellen Yeats
Objective: This study aims to investigate and correct acoustic phase aberration through soft tissues to improve transabdominal histotripsy therapy.
Part I. Simulation–based Investigation
Background: Histotripsy relies on generating a robust bubble cloud at a specified target location in tissue (like a tumor). To produce the requisite high pressures at the target, histotripsy transducers are large and geometrically focused (spherically curved). In a homogeneous medium with constant speed of sound, waves from the curved aperture will arrive synchronously in phase) at the geometric center to create a sharp acoustic focus with large pressure amplitude. However, in a therapy scenario, the waves must pass through a coupling water bath and the body, which is composed of different tissue types. The resulting spatial variations in the speed of sound cause waves to arrive out of phase at the geometric center, which weakens, enlarges, and displaces the focus. This focal distortion can reduce the efficacy and safety of histotripsy therapy by decreasing the maximum field pressure and shifting the location of the bubble cloud away from the target.
Methods: To understand how phase aberration affects focusing in transabdominal histotripsy therapy, we simulated wave propagation using human data from 10 abdominal CT scans. Abdominal images were segmented into 5 tissue types: bone, cartilage, skin, fat, and other soft tissue (e.g., muscle and liver). The speed of sound of each tissue type and water is given in Table 1. A custom-built transducer from our lab designed for hepatic tumor ablation was simulated targeting the liver (see Figure 1).
Results: The map in Fig. 2 (a) shows that the average arrival time difference to the geometric center is 0.52 us. Notably, sound from the transducer center arrives > 1 us later than sound from the transducer edges. These transabdominal arrival delays are large compared to one acoustic cycle of the histotripsy pulse (1.3 us). The effect of these large delays is illustrated by Figs. 2 (b) and (c), which show the focus in the liver with and without correction of the phase aberration, respectively. Correction of the phase aberration made a smaller, higher amplitude simulated focus exactly at the geometric center (the target). The uncorrected focus is weaker, larger, irregularly shaped, and displaced from the target by ~1mm in the radial dimensions of the transducer (shown) and by another 6 mm along the transducer axial dimension (not shown).
Conclusion: The results of this study suggest that phase aberration correction could improve the efficacy and safety of transabdominal histotripsy therapy.
Part II. Acoustic Emission–Based Aberration Correction
Background: When the rarefactional (negative) pressure amplitude exceeds a threshold (26 – 30 MPa) in water–based tissue, nanometer–sized gas pockets are excited and act as nuclei for the generation of cavitation. As the bubbles form, they expand in size from a few nanometers to several tens of micrometers. This rapid expansion generates a pressure shockwave – a sharp, high bandwidth signal that can be detected by ultrasound transducers. This signal originates from the focus (the location of the bubble cloud) and propagates out radially, passing through the same path as the sound emitted by the transducer, but in reverse. Therefore, this expansion shockwave signal contains phase information that can be used to correct aberration.
Methods: To assess the efficacy of using the bubble expansion shockwave to correct aberration, a receive–capable histotripsy array with 112 individually deployable 500–kHz transducer elements was designed and built in–house (see Fig. 3). The array aperture was large with low F# (large curvature), which placed outer elements at high incidence angles to the porcine abdominal wall aberrator set in the sound path, as shown in Fig. 3 (A). First, bubble expansion was investigated optically. A camera and light source were used to capture high speed images of the expanding bubbles.
Second, the efficacy of aberration correction based on receiving the expansion shockwave was tested. Cavitation was generated through the tissue aberrator. The expansion shockwave signals were received at the array elements and processed. Then, the detected phase shifts were compensated by delaying
the deployment of each element by an appropriate duration. The pressure recovered by this correction was measured and compared to the performance of a gold standard (hydrophone measurement).
Results: The number of bubbles (and thus emission shockwaves) depends on the rarefactional pressure amplitude (see Fig. 4). The first-arriving shockwave emitted by the cloud (shown in red in Fig. 4 (D)) originated ~3 mm closer to the transducer than the geometric focus (blue). To avoid overlapping signals from multiple shockwaves, signal from the first shockwave was isolated and used to determine the phase distribution.
Figure 5 shows one–dimensional maps of the pressure around the focus in the radial axes (X and Y) and depth axis (2) of the transducer with acoustic cavitation emission (ACE) aberration correction, hydrophone aberration correction, and no aberration correction. ACE aberration correction improved the pressure amplitude by –21% versus –55% for the hydrophone.
For a fixed transmission pressure from the transducer, aberration by abdominal wall tissues leads to a weaker, shifted bubble cloud. Ideal correction with a hydrophone placed at the geometric focus leads to a strong bubble cloud centered exactly at the geometric focus. Correction with ACE also improves the size of the bubble cloud but slightly worsens the focal shift in the depth direction. (See Fig. 6).
Conclusion: This was the first study to use cavitation emission signals to correct phase aberration of histotripsy. We showed that soft tissue aberration correction with ACE could recover significant pressure for histotripsy therapy. ACE correction can improve the efficiency of histotripsy therapy in situations where soft tissue aberration severely weakens the bubble cloud.
Use of the bubble emission shockwave had some disadvantages. Closely overlapping shockwaves from multiple bubbles complicate arrival time detection. The first-arriving shockwave can be used for
detection but originates several millimeters closer to the transducer than the geometric focus. Detected arrival times are relative to this displaced origin. Therefore, the resulting correction shifts the bubble cloud closer to the transducer by the same distance.
To address these issues, future work will study signals from bubble collapse. Shockwave emission by a collapsing bubble cloud is a singular event that originates at the cloud center. This sharper, more centralized acoustic signal could improve ACE aberration correction by improving arrival time detection and preventing additional displacement of the focus.
Referenced Publication: Macoskey, Jonathan J et al. “Soft-Tissue Aberration Correction for Histotripsy.” IEEE transactions on ultrasonics, ferroelectrics, and frequency control vol. 65,11 (2018): 2073-2085. doi:10.1109/TUFFC.2018.2872727