M. Pernot

Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans

Developing minimally invasive brain surgery by high-intensity focused ultrasound beams is of great interest in cancer therapy. However, the skull induces strong aberrations both in phase and amplitude, resulting in a severe degradation of the beam shape. Thus, an efficient brain tumor therapy would require an adaptive focusing, taking into account the effects of the skull. In this paper, we will show that the acoustic properties of the skull can be deduced from high resolution CT scans and used to achieve a noninvasive adaptive focusing. Simulations have been performed with a full 3-D finite differences code, taking into account all the heterogeneities inside the skull. The set of signals to be emitted in order to focus through the skull can thus be computed. The complete adaptive focusing procedure based on prior CT scans has been experimentally validated. This could have promising applications in brain tumor hyperthermia but also in transcranial ultrasonic imaging.

In Vivo Quantitative Mapping of Myocardial Stiffening and Transmural Anisotropy During the Cardiac Cycle

Shear wave imaging was evaluated for the in vivo assessment of myocardial biomechanical properties on ten open chest sheep. The use of dedicated ultrasonic sequences implemented on a very high frame rate ultrasonic scanner (>; 5000 frames per second) enables the estimation of the quantitative shear modulus of myocardium several times during one cardiac cycle. A 128 element probe remotely generates a shear wave thanks to the radiation force induced by a focused ultrasonic burst. The resulting shear wave propagation is tracked using the same probe by cross-correlating successive ultrasonic images acquired at a very high frame rate. The shear wave speed estimated at each location in the ultrasonic image gives access to the local myocardial stiffness (shear modulus μ). The technique was found to be reproducible (standard deviation <; 3%) and able to estimate both systolic and diastolic stiffness on each sheep (respectively μdias ≈ 2 kPa and μsyst ≈ 30 kPa). Moreover, the ability of the proposed method to polarize the shear wave generation and propagation along a chosen axis permits the study the local elastic anisotropy of myocardial muscle. As expected, myocardial elastic anisotropy is found to vary with muscle depth. The real time capabilities and potential of Shear Wave Imaging using ultrafast scanners for cardiac applications is finally illustrated by studying the dynamics of this fractional anisotropy during the cardiac cycle.

Monitoring Thermally-Induced Lesions with Supersonic Shear Imaging

Thermally-induced lesions are generally stiffer than surrounding tissues. We propose here to use the supersonic shear imaging technique (SSI) for monitoring high-intensity focused ultrasound (HIFU) therapy. This new elasticity imaging technique is based on remotely creating shear sources using an acoustic radiation force at different locations in the medium. In these experiments, an HIFU probe is used to generate lesions in fresh tissue samples. A diagnostic transducer, controlled by our ultrafast scanner, is located in the therapeutic probe focal plane. It is used for both generating the shear waves and imaging the resulting propagation at frame rates reaching 5,000 images/s. Movies of the shear wave propagation can be computed off-line. The therapeutic and imaging sequences are interleaved and a set of wave propagation movies is performed during the heating process. From each movie, elasticity estimations have been performed using an inversion algorithm. It demonstrates the feasibility of detecting and quantifying the hardness of HIFU-induced lesions using SSI.

Arterial wall elasticity: State of the art and future prospects

Peripheral vascular disease is a frequently occurring disease and is most often caused by atherosclerosis and more rarely by anomalies of the collagen or other components of the arterial wall. Arterial stiffness problems form one of the precursor phenomena of peripheral vascular disease, and in the case of atherosclerosis represents an independent risk marker for the occurrence of cardiovascular disease. The first techniques, developed to evaluate arterial stiffness, use indirect measurements such as pulse wave velocity or the analysis of variations in pressure and volume to estimate arterial wall stiffness. Techniques based on the pulse wave lack precision because they assume that arterial stiffness is uniform throughout the path of the pulse wave, and that it is constant throughout the cardiac cycle. Moreover, measuring the velocity of the pulse wave may be less precise in certain pathological situations: metabolic syndrome, obesity, large chest, mega-dolico artery. Techniques based on the analysis of variations in pressure and in volume do not accurately measure blood pressure, which can only be taken externally. In addition, these techniques require dedicated equipment, which is not reimbursed by the French health care system, and which is cumbersome to use (especially for techniques based on variation in pressure) in clinical practice. This explains why these two techniques are not used in clinical practice. Ultrafast echography is a new ultrasound imaging method that can record up to 10,000 images per second. This high temporal resolution makes it possible to measure the velocity of the local pulse wave and arterial wall stiffness thanks to the remote palpation carried out by shear wave. The ease of use and the accuracy of these two techniques suggest that these diagnostic applications will play a significant role in vascular pathology in the future. It is possible in real time, using a traditional vascular ultrasound probe, to make an accurate assessment of local arterial stiffness and of its variation during the cardiac cycle. This technological breakthrough will probably improve phenotype evaluation of patients suffering from vascular diseases, to more effectively evaluate the cardiovascular risk for patients, at primary and secondary prevention level, and to carry out broad epidemiological studies on cardiovascular risks.

Cardiac shear-wave elastography using a transesophageal transducer: application to the mapping of thermal lesions in ultrasound transesophageal cardiac ablation.

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesions extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions. First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle (n = 11) and mapped (n = 7). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n  =  3), then atrial (left, n = 2) and ventricular (left n = 1, right n = 1) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE. During the cardiac cycle stiffness varied from 0.5   ±   0.1 kPa to 6.0   ±   0.3 kPa in the atrium and from 1.3   ±   0.3 kPa to 13.5   ±   9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3   ±   5.5 kPa (versus 4.4   ±   1.6 kPa before ablation) in the chicken breast, to 30.3   ±   10.3 kPa (versus 12.2   ±   4.3 kPa) in the atria and to 73.8   ±   13.9 kPa (versus 21.2   ±   3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm(2) in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1:  -0.8 mm; third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm(2) and a median of 0.2 mm (Q1:  -2.7 mm; Q3: 2.7 mm) for a MSE of 11.1 mm(2) from gross pathology. We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias.

High Power Phased Array Prototype for Clinical High Intensity Focused Ultrasound : Applications to Transcostal and Transcranial Therapy

Bursts of focused ultrasound energy three orders of magnitude more intense than diagnostic ultrasound became during the last decade a noninvasive option for treating cancer from breast to prostate or uterine fibroid. However, many challenges remain to be addressed. First, the corrections of distortions induced on the ultrasonic therapy beam during its propagation through defocusing obstacles like skull bone or ribs remain today a technological performance that still need to be validated clinically. Secondly, the problem of motion artifacts particularly important for the treatment of abdominal parts becomes today an important research topic. Finally, the problem of the treatment monitoring is a wide subject of interest in the growing HIFU community. For all these issues, the potential of new ultrasonic therapy devices able to work both in Transmit and Receive modes will be emphasized. A review of the work under achievement at L.O.A. using this new generation of HIFU prototypes on the monitoring, motion correction and aberrations corrections will be presented.

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.

4J-5 A 3D Elastography System Based on the Concept of Ultrasound-Computed Tomography for In Vivo Breast Examination

Elastography holds great promises for the additional characterization of lesions especially in the domain of breast cancer diagnosis. Most ultrasound based approaches have so far been limited to a one dimensional (1D) or at most two dimensional (2D) displacement estimation in one plane. This leads for the general case to sparse data which cannot be used to solve the full three dimensional (3D) wave equation in an unbiased manner. For instance contributions from the compressional wave cannot be removed via application of the curl operator. In order to overcome this limitation we developed an ultrasound based elastography system which uses the concept of computed tomography for data acquisition in combination with 2D vector displacement estimation within the plane of the ultrasound beam. The vector displacement estimation is achieved using the concept of adaptive subapertures during the receive beamforming process. The object of interest is scanned using a conventional ultrasonic probe (4 MHz, 128 elements) from different directions on a circular orbit. The transducer is translated perpendicular to the orbit (~10 times) for each angle which leads to several block datasets (~30 blocks) each containing 2D displacement information. Thereby, the displacement of each voxel within the object is measured several times from different directions. This provides high resolution volumic 3D displacement fields after regridding each dataset from polar to Cartesian coordinates. The data acquisition system is contained within a water tank underneath a standard breast biopsy table. This enables in vivo measurements with the patient in prone position. Thereby, the 3D acquisition as already developed in the area of magnetic resonance elastography (MRE), is brought to the ultrasonic field. Initial phantom experiments were conducted with steady state mechanical excitation at 150 Hz. Inclusions are clearly visible in the complex shear modulus as reconstructed from inverting the full 3D wave equation. Taking benefit of the ultrafast acquisition speed of our ultrasound system, the proposed method allows to measure volumic datasets within clinically acceptable time. The method provides for each voxel of the 3D volume the frequency dependence of the complex shear modulus which in turn is linked to the underlying rheology of the material. This represents the proof of concept for a spectroscopic approach of elastography suitable for clinical application. The system enables the study of rheological properties of tumors which should further extend the diagnostic gain of elastography

Ultrasonic transcranial brain therapy: first in vivo clinical investigation on 22 sheep using adaptive focusing

A high power prototype dedicated to trans-skull therapy has been tested in vivo on 22 sheep. An echographic array was inserted in the therapeutic array in order to perform real time monitoring of the treatment. In one set of experiments, 10 sheep were treated and sacrificed immediately after treatment. On half of these animals, a complete craniotomy was performed in order to get reference models. On the other animals, a minimally invasive surgery was performed to insert a hydrophone at the target inside the brain. A time reversal experiment was then conducted through the skull with the therapeutic array to treat the targeted point. Hyperechogeneicity was clearly visible on the sonographic system for all animals with a complete craniotomy. Without craniotomy, the ultrasonic image was distorted, but the hydrophone location was visible, allowing a rough positioning of the therapeutic device. More accurate positioning was then obtained by cross correlating the signals received by the elements in the therapeutic device. Trans-skull treatment could be achieved with phase aberration correction and electronic beam steering, not only at the geometrical focus, but also 2 cm away in all directions. In a second series of experiments, 12 animals were divided into three groups and sacrificed respectively one, two and three weeks after treatment. The evolution of the targeted region was checked each week using magnetic resonance imaging and CT scans. Finally, histological examination was performed to confirm tissue damage. These in vivo experiments highlight the strong potential of high power transcranial time reversal technology.

Prediction of the skull overheating during high intensity focused ultrasound transcranial brain therapy

Ultrasound brain therapy is currently limited by the strong phase and amplitude aberrations induced by the heterogeneities of the skull. However, the development of aberration correction techniques has made it possible to correct the beam distortion induced by the skull and to produce a sharp focus in the brain. Moreover, using the density of the skull bone that can be obtained with high-resolution CT scans, the corrections needed to produced this sharp focus can be calculated using ultrasound propagation models. We propose a model for computing the temperature elevation in the skull during high intensity focused ultrasound (HIFU) transcranial therapy. Based on CT scans, the wave propagation through the skull is computed with 3D finite difference wave propagation software. The acoustic simulation is combined with a 3D thermal diffusion code and the temperature elevation inside the skull is computed. Finally, the simulation is validated experimentally by measuring the temperature elevation in several locations of the skull.