Self-adaptive ultrasonic beam amplifiers: application to transcostal shock wave therapy.

Ultrasound shock wave therapy is increasingly used for non-invasive surgery. It requires the focusing of very high pressure amplitude in precisely controlled focal spots. In transcostal therapy of the heart or the liver, the high impedance mismatch between the bones and surrounding tissues gives rise to strong aberrations and attenuation of the therapeutic wavefront, with potential risks of injury at the tissue-bone interface. An adaptive propagation of the ultrasonic beam through the intercostal spaces would be required. Several solutions have been developed so far, but they require a prior knowledge of the patient's anatomy or an invasive calibration process, not applicable in clinic. Here, we develop a non-invasive adaptive focusing method for ultrasound therapy through the ribcage using a time reversal cavity (TRC) acting as an ultrasonic beam amplifier. This method is based on ribcage imaging through the TRC and a projection orthogonally to the strongest identified reflectors. The focal pressure of our device was improved by up to 30% using such self-adaptive processing, without degrading the focal spots size and shape. This improvement allowed lesion formation in an Ultracal® phantom through a ribcage without invasive calibration of the device. This adaptive method could be particularly interesting to improve the efficiency and the safety of pulsed cavitational therapy of the heart or the liver.

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis. To reproduce venous thrombosis conditions, human whole blood was allowed to clot by stasis in silicone tubes (6 mm internal diameter) at a 30 cm H2O pressure, maintained during the whole experiment. We engineered an ultrasound device composed of dual 2.25 MHz transducers centered around a 6 MHz imaging probe. A therapeutic focus was generated at a 3.2 cm depth from the probe. Thrombotripsy was performed by longitudinally scanning the thrombus at three different speeds: 1 mm s-1 (n = 6); 2 mm s-1 (n = 6); 3 mm s-1 (n = 12). Restored outflow was measured every three passages. Filters were placed to evaluate the debris size. Twenty-four occlusive thrombi, of 2.5 cm mean length and 4.4 kPa mean stiffness, were studied. Flow restoration was systematically obtained by nine subsequent passages (4.5 min maximum). By varying the device's speed, we found an optimal speed of 1 mm s-1 to be efficient for effective recanalization with 90 s (three passages). Within 90 s, flow restoration was of 80, 62 and 74% at respectively 1, 2 and 3 mm s-1. For all groups, cavitation cloud drilled a 1.7 mm mean diameter channel throughout the clot. Debris analysis showed 92% of debris <10 µm, with no fragment > 200 µm.

A 3D time reversal cavity for the focusing of high-intensity ultrasound pulses over a large volume.

Shock wave ultrasound therapy techniques, increasingly used for non-invasive surgery, require extremely high pressure amplitudes in precise focal spots, and large high-power transducers arranged on a spherical shell are usually used to achieve that. This solution allows limited steering of the beam around the geometrical focus of the device at the cost of a large number of transducer elements, and the treatment of large and moving organs like the heart is challenging or impossible. This paper validates numerically and experimentally the possibility of using a time reversal cavity (TRC) for the same purpose. A 128-element, 1 MHz power transducer combined with different multiple scattering media in a TRC was used. We were able to focus high-power ultrasound pulses over a large volume in a controlled manner, with a limited number of transducer elements. We reached sufficiently high pressure amplitudes to erode an Ultracal® target over a 10 cm2 area.

In vivo real-time cavitation imaging in moving organs.

The stochastic nature of cavitation implies visualization of the cavitation cloud in real-time and in a discriminative manner for the safe use of focused ultrasound therapy. This visualization is sometimes possible with standard echography, but it strongly depends on the quality of the scanner, and is hindered by difficulty in discriminating from highly reflecting tissue signals in different organs. A specific approach would then permit clear validation of the cavitation position and activity. Detecting signals from a specific source with high sensitivity is a major problem in ultrasound imaging. Based on plane or diverging wave sonications, ultrafast ultrasonic imaging dramatically increases temporal resolution, and the larger amount of acquired data permits increased sensitivity in Doppler imaging. Here, we investigate a spatiotemporal singular value decomposition of ultrafast radiofrequency data to discriminate bubble clouds from tissue based on their different spatiotemporal motion and echogenicity during histotripsy. We introduce an automation to determine the parameters of this filtering. This method clearly outperforms standard temporal filtering techniques with a bubble to tissue contrast of at least 20 dB in vitro in a moving phantom and in vivo in porcine liver.

Highly sensitive magneto-motive photoacoustic and ultrasound (PAUS) imaging with cyclic excitations.

Highly specific molecular imaging with photoacoustics (PA) must suppress background endogenous signals while maintaining signals from target nanoagents. Magneto-motive PA was introduced to perform motion-based background suppression using a low frequency magnetic field. Previous studies show suppression based on displacement magnitude can suffer if significant physiological motion is present. This limitation can be overcome using cyclic magneto-motive PA (cmmPA), where multiple cycles of an ac magnetic field are used and the coherence of detected displacements is the retrieved information. In this paper, we show a method to enhance the magnetic response of an electromagnet specifically for cmmPA. Several magnetic frequencies were tested and a simple model is proposed to describe displacement frequency dependence. By choosing optimal parameters based on this model, we show that the technique can detect a low number of tagged cells using either US-based or PA-based displacement estimation. In addition, robustness to physiological motion is demonstrated in a moving phantom.

Global approach for transient shear wave inversion based on the adjoint method: a comprehensive 2D simulation study.

Shear wave imaging (SWI) maps soft tissue elasticity by measuring shear wave propagation with ultrafast ultrasound acquisitions (10 000 frames s(-1)). This spatiotemporal data can be used as an input for an inverse problem that determines a shear modulus map. Common inversion methods are local: the shear modulus at each point is calculated based on the values of its neighbour (e.g. time-of-flight, wave equation inversion). However, these approaches are sensitive to the information loss such as noise or the lack of the backscattered signal. In this paper, we evaluate the benefits of a global approach for elasticity inversion using a least-squares formulation, which is derived from full waveform inversion in geophysics known as the adjoint method. We simulate an acoustic waveform in a medium with a soft and a hard lesion. For this initial application, full elastic propagation and viscosity are ignored. We demonstrate that the reconstruction of the shear modulus map is robust with a non-uniform background or in the presence of noise with regularization. Compared to regular local inversions, the global approach leads to an increase of contrast (∼+3 dB) and a decrease of the quantification error (∼+2%). We demonstrate that the inversion is reliable in the case when there is no signal measured within the inclusions like hypoechoic lesions which could have an impact on medical diagnosis.