Collagenous tissues, such as tendon, have proven resistant to mechanical fractionation by histotripsy. Evidence on B-mode ultrasound images suggests the successful creation of boiling bubbles and/or cavitation bubble clouds in these collagenous tissues; however, the oscillation and collapse of the bubbles does not result in tissue fractionation. Here, tissue-mimicking collagen gels were placed at the focus of a 1.5-MHz HIFU transducer and insonified at various pulse lengths and repetition frequencies. Cavitation activity was monitored passively with a Philips/ATL L7-4 imaging transducer (Bothell, WA USA) and Vantage® research ultrasound system (Verasonics, Kirkland, WA, USA) and compared to high-speed photographs (Photron Nova S-9, Tokyo, Japan). Preliminary results in the tissue-mimicking collagen phantoms show violent cavitation activity and rapid gel fractionation with conventional histotripsy parameters, which is dissimilar to what is observed in highly collagenous tissues. To address this limitation, we will explore phantoms with superior fiber alignment, such as fibrin gels, which will allow for evaluation of histotripsy parameters that promote mechanical fractionation in highly collagenous tissues. [Work supported by NIH R21EB027886 and NSF GRF #DGE1255832.]
Focused ultrasound (fUS) therapy can induce controllable mechanical damage through bubble creation, oscillation, and collapse. However, highly collagenous tissues like tendon are resistant to mechanical fractionation with fUS. Our objective is to histologically evaluate whether fUS-induced mechanical disruption is achievable in rat tendon. Ex vivo Achilles (AT) and supraspinatus (ST) tendons were exposed to 1.5 MHz pulses of 0.1–10 ms repeated at 1–100 Hz for 15–60 s with peak pressures p+ = 69 MPa, p− = 24 MPa. B-mode ultrasound was used to monitor hyperechogencity during treatment. Samples were stained with Hematoxylin and Eosin (H&E) or alpha-nicotinamide dinucleotide diaphorase (αNADH-d). Results showed successful bubble creation for all samples; however, all samples did not show histological injury. Samples treated with 10-ms pulses at 1 Hz for 15 s displayed only slight disruption (2/5 AT, 2/5 ST). When treatment time increased to 30 s, thermal injury dominated over mechanical effects. Shorter pulse lengths (1 ms at 10 Hz; 0.1 ms at 100 Hz) resulted in localized fiber separation (5/10 AT, 2/10 ST). Future work will investigate how fUS influences mechanical properties of tendon and whether it can induce a healing response in vivo. [Work supported by NIH NIBIB EB027886; NSF GRFP DGE1255832 (Smallcomb).]
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