Taboos and opportunities in sonothrombolysis for stroke

Figures & data

Figure 1. Attenuation per unit length plotted against ultrasound carrier frequency in human temporal bone as given in recent publications (blue diamonds and line) [36], [72], [73]. Symptomatic intracerebral haemorrhage rates in sonothrombolysis trials (controlled and uncontrolled) plotted against ultrasound carrier frequency (red dots) [1]. Grey-filled squares illustrate acoustic cavitation thresholds from an experimental measurement in different blood sample combinations at 120 kHz pulsed ultrasound [27]. It should be mentioned that acoustic cavitation thresholds vary depending on media, emitting frequencies and acoustic parameters (e.g. with lower frequency and continuous wave ultrasound, the threshold for any cavitation in blood or any other biological media will decrease). Higher attenuation through the skull with high frequency ultrasound may lead to lower acoustic pressures inside the targeted region (e.g. predicted acoustic pressure for the CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), trial: 0.07 MPa) [43], whereas lower absorption of the skull with low frequency ultrasound may yield acoustic pressures well above the inertial cavitation threshold putting the brain at higher risk of bleeding (e.g. predicted acoustic pressure for the TRUMBI trial: 0.27–1.2 MPa) [57].

Table I.  Proposed guidelines for reporting certain ultrasound parameters in experimental and clinical sonothrombolysis studies (if applicable) (adapted from Mark Schafer [74]).

Ultrasound parameter	Unit
Peak rarefaction pressure	MPa
Frequency, and any modulation	Hz (MHz or kHz)
ISPTA intensity (for comparison to FDA limits)	W/cm^2
Total power	W
Pulse duration or CW	s (and number of cycles)
Pulse repetition frequency	Hz
Beam width −6/−12 dB	mm
Aperture size and shape	mm
Focal distance (or unfocused)	mm
Distance from transducer to region of interest	mm
Mechanical/thermal index	number

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