Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation

Abstract

Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated a cavitation cloud can be formed by a single pulse with one high amplitude negative cycle, when the negative pressure amplitude directly exceeds a pressure threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in water-based tissues is determined by the properties of the water inside the tissue and changes in tissue stiffness or ultrasound frequency will have a minimal impact on the histotripsy intrinsic threshold. To test this hypothesis, the histotripsy intrinsic threshold was investigated both experimentally and theoretically. The probability of cavitation was measured by subjecting tissue phantoms with adjustable mechanical properties and ex vivo tissues to a histotripsy pulse of 1–2 cycles produced by 345 kHz, 500 kHz, 1.5 MHz, and 3 MHz histotripsy transducers. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured vs. pressure amplitude. The results demonstrated that the intrinsic threshold (the negative pressure at which probability=0.5) is independent of stiffness for Young’s moduli (E) < 1 MPa with only a small increase (~2–3 MPa) in the intrinsic threshold for tendon (E=380 MPa). Additionally, results for all samples showed only a small increase of ~2–3 MPa when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold was measured to be between 24.7–30.6 MPa for all samples and frequencies tested in this study. Overall, the results of this study indicate that the intrinsic threshold to initiate a histotripsy bubble cloud is not significantly impacted by tissue stiffness or ultrasound frequency in hundreds of kHz to MHz range.

Pressure Pulse Distortion by Needle and Fiber-Optic Hydrophones due to Nonuniform Sensitivity

“…Common robust fiber-optic hydrophones have sensitive element sizes around d = 100 μm [10, 17, 21, 23, 62]. Highly nonlinear waveforms in combination with values of d /λ 0 near 0.1–0.4 can result in considerable potential distortion in peak compressional pressure (see Fig.…”

“…6, lower right panel). Such values are achievable in well-validated, extremely promising approaches including histotripsy ( e.g., d /λ 0 ≈ 0.1 at 1.5 MHz [23] and d /λ 0 ≈ 0.07 at 1 MHz [62]) and other HITU applications ( e.g., d /λ 0 ≈ 0.14 at 2 MHz [17] and d /λ 0 ≈ 0.08 at 1.2 MHz [21]).…”

“…In addition, some needle [5] and fiber-optic [6–14] hydrophones are more robust for high-intensity therapeutic ultrasound (HITU) measurements than most membrane hydrophones, although robust membrane hydrophone designs also have been proposed [15, 16]. Fiber–optic hydrophones have been used extensively for calibration of HITU [17–23] and lithotripsy [24] systems. Some fiber optic hydrophones have exceptional spatial resolution on the order of 100 μm or less, far superior to most membrane hydrophones.…”

“…Since the fiber-optic hydrophone core typically has far higher characteristic impedance than the surrounding fluid, it may be accurately modeled as a rigid disk [31]. This model applies to many fiber-optic hydrophones, such as those commonly used in HITU [17, 18, 21–23] and lithotripsy [24]. Other fiber-optic hydrophones, such as those based on multi-layer [32], distributed Bragg reflector [33], Fabry-Perot interferometer [34–36] and other [37] designs, have a more complex response than the rigid, semi-infinite rods model predicts.…”

The influence of gas diffusion on bubble persistence in shock-scattering histotripsy

“…7 The discrepancy may be due to the 20 nm nucleus considered in this study in comparison to the 2-20 lm nucleus considered previously. Nanoscale nuclei are intrinsic to the tissue targets of histotripsy, 19,20 whereas micrometer-sized nuclei can be harbored on a kidney stone. 21 Despite the difference in equilibrium size between the two sources of nuclei, the bubbles computed in this study are large enough to be visualized with B-mode ultrasound.…”