Investigation of waveform modulation and amplitude for the treatment of tendinopathies

Tendon is typically resistant to fractionation by focused ultrasound (FUS). Prior work showed that combining tendinopathy and FUS-induced heating increased tendon susceptibly to fractionation but also caused unwanted thermal necrosis. Here, we investigated waveform modulation and pressure amplitude for tendinopathy using 1.50- and 2.45-MHz FUS. Ex vivo bovine tendons were injected with collagenase to induce tendinopathy and treated with single-amplitude waveforms (low: p+≤52 MPa/p-≤18 MPa; mid: p+≤108 MPa/p-≤27 MPa; or high: p+≤127 MPa/p-≤35 MPa) of 1–5 ms) or hybrid waveforms (low, mid, or high amplitude for 1–5 ms before lowering to p+≤19 MPa/p-≤11 MPa for 5–9 ms). Treatments were monitored in real time using passive cavitation detection and halted when the waveform smoothed for 10 consecutive pulses or when the treatment reached 5 min, whichever came first. Samples were analyzed histologically. Results showed that amplitude alone did not impact the amount of fiber fraying and disruption, but waveform modulation in combination with amplitude affected the amount of damage observed. At mid and high amplitudes, hybrid waveforms produced more fiber fraying and disruption than single-amplitude waveforms; there was no difference between waveform types at low amplitudes. These results suggest that waveform modulation at mid to high amplitudes should be investigated further for successful fractionation in the treatment of tendinopathy. [Work supported by NIH-R01EB032860.]