Abstract
High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive.In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5–35 dB for peak negative pressures between 1.19–3.19 ± 0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2–2.71 ± 0.01 MPa at a fluence of 3.4 mJ . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination.Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as providing the ability to identify and treat small multi-focal cancerous regions with minimal damage to surrounding healthy tissue.
Highlights
High intensity focused ultrasound (HIFU), or focused ultrasound surgery (FUS), is a non-invasive technique that is used to generate coagulative necrosis through localised thermal ablation in subcutaneous tissues
In this example the laser fluence was 2.1 mJ cm−2, where applicable, with two different P−s (1.43 or 2.34 MPa).Where broadband emissions are present the two key differences were that for the larger pressure, both the duration and amplitude are increased, and the time of flight for these emissions both correspond to the synchronisation of the laser and HIFU pulses in the target region
In this study we have demonstrated, in vitro, the capability of using AuNRs combined with HIFU and pulsed laser illumination for both imaging and enhanced thermal denaturation
Summary
High intensity focused ultrasound (HIFU), or focused ultrasound surgery (FUS), is a non-invasive technique that is used to generate coagulative necrosis through localised thermal ablation in subcutaneous tissues (ter Haar 1995). The general term of ‘cavitation activity’ covers a range of phenomena that can be dependent on the exposure parameters and/or target medium It is commonly defined as the presence and activity of acoustic cavitation (Neppiras 1980, 1984) and/or thermally mediated gas pocket formation, through exsolution or vaporisation (McLaughlan et al 2010a). When the duty cycle is reduced to neglect any effects from heating, the peak negative pressure (P−) required to generate detectable acoustic cavitation activity is typically greater than 10 MPa (Gateau et al 2011, Arnal et al 2017) This approach termed histotripsy (Hall et al 2007) primarily relies on mechanical damage from bubble activity to cause tissue destruction without any significant heating to the tissue. Whereas the technique termed boiling histotripsy (Wang et al 2013) sits between the predominately thermal or mechanical approaches for localised tissue destruction
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