Laurent Marsac

Non-invasive transcranial ultrasound therapy based on a 3D CT scan: protocol validation and in vitro results

A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head.

PURPOSE This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. METHODS Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. RESULTS The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. CONCLUSIONS The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.

Targeting accuracy of transcranial magnetic resonance-guided high-intensity focused ultrasound brain therapy: a fresh cadaver model.

OBJECT This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads. METHODS Eighteen heads of fresh human cadavers were removed with a dedicated protocol preventing intracerebral air penetration. The MR images allowed determination of the ultrasonic target: a part of the thalamic nucleus ventralis intermedius implicated in essential tremor. Osseous aberrations were corrected with simulation-based time reversal by using CT data from the heads. The ultrasonic session was performed with a 512-element phased-array transducer system operating at 1 MHz under stereotactic conditions with thermometric real-time MR monitoring performed using a 1.5-T imager. RESULTS Dissection, imaging, targeting, and planning have validated the feasibility of this human cadaver model. The average temperature elevation measured by proton resonance frequency shift was 7.9°C ± 3°C. Based on MRI data, the accuracy of MRgHIFU is 0.4 ± 1 mm along the right/left axis, 0.7 ± 1.2 mm along the dorsal/ventral axis, and 0.5 ± 2.4 mm in the rostral/caudal axis. CONCLUSIONS Despite its limits (temperature, vascularization), the human cadaver model is effective for studying the accuracy of MRgHIFU brain therapy. With the 1-MHz system investigated here, there is millimetric accuracy.

Transcranial Ultrasonic Therapy Based on Time Reversal of Acoustically Induced Cavitation Bubble Signature

Brain treatment through the skull with high-intensity focused ultrasound can be achieved with multichannel arrays and adaptive focusing techniques such as time reversal. This method requires a reference signal to be either emitted by a real source embedded in brain tissues or computed from a virtual source, using the acoustic properties of the skull derived from computed tomography images. This noninvasive computational method focuses with precision, but suffers from modeling and repositioning errors that reduce the accessible acoustic pressure at the focus in comparison with fully experimental time reversal using an implanted hydrophone. In this paper, this simulation-based targeting has been used experimentally as a first step for focusing through an ex vivo human skull at a single location. It has enabled the creation of a cavitation bubble at focus that spontaneously emitted an ultrasonic wave received by the array. This active source signal has allowed 97 ± 1.1% of the reference pressure (hydrophone-based) to be restored at the geometrical focus. To target points around the focus with an optimal pressure level, conventional electronic steering from the initial focus has been combined with bubble generation. Thanks to step-by-step bubble generation, the electronic steering capabilities of the array through the skull were improved.

Random calibration for accelerating MR-ARFI guided ultrasonic focusing in transcranial therapy

Transcranial focused ultrasound is a promising therapeutic modality. It consists of placing transducers around the skull and emitting shaped ultrasound waves that propagate through the skull and then concentrate on one particular location within the brain. However, the skull bone is known to distort the ultrasound beam. In order to compensate for such distortions, a number of techniques have been proposed recently, for instance using Magnetic Resonance Imaging feedback. In order to fully determine the focusing distortion due to the skull, such methods usually require as many calibration signals as transducers, resulting in a lengthy calibration process. In this paper, we investigate how the number of calibration sequences can be significantly reduced, based on random measurements and optimization techniques. Experimental data with six human skulls demonstrate that the number of measurements can be up to three times lower than with the standard methods, while restoring 90% of the focusing efficiency.

Keyhole acceleration for magnetic resonance acoustic radiation force imaging (MR ARFI)

MR ARFI measures the displacement induced by the ultrasonic radiation force and provides the location of the focal spot without significant heating effects. Displacements maps obtained with MR ARFI provide an indirect estimation of the acoustic beam intensity at the target. This measure is essential for dose estimation prior to focused ultrasound treatments (FUS) and adaptive focusing procedures of MR-guided transcranial and transribs FUS. In the latter case, the beam correction is achieved by maximizing the displacement at focus. A significant number of serial MR ARFI images are required and thus, a partial k-space updating method, such as keyhole appears as a method of choice. The purpose of this work is to demonstrate via simulations and experiments the efficiency of the keyhole technique combined with a two-dimensional spin-echo MR ARFI pulse sequence. The method was implemented in an ex vivo calf brain taking advantage of the a priori knowledge of the focal spot profile. The coincidence of the phase-encoding axis with the longest axis of the focal spot makes the best use of the technique. Our approach rapidly provides the focal spot localization with accuracy, and with a substantial increase to the signal-to-noise ratio, while reducing ultrasound energy needed during MR-guided adaptive focusing procedures.

Adaptive focusing of transcranial therapeutic ultrasound using MR Acoustic Radiation Force Imaging in a clinical environment

Background: In order to focus ultrasound beams through aberrating layers such as fat or bones, adaptive focusing techniques have been proposed to improve the focusing, mostly based on the backscattered echoes. We recently proposed an energy-based technique with the sole requirement being knowledge of the acoustic intensity at the desired focus. Here, Magnetic Resonance-Acoustic Radiation Force Imaging (MR-ARFI) is used to map the displacement induced by the radiation force of a focused ultrasound beam. As the maximum displacement is obtained with the best corrected beam, such a measurement can lead to aberration correction. Material and methods: Proof of concept experiments were previously shown in a small animal MR at 7 T using a 64-elements linear phased array operating at 6 MHz. Optimal refocusing was then obtained through numerical and physical aberrating layers. This work is extended here in a clinical Philips 1.5 T Achieva scanner. The HIFU beam is generated using a 512 elements US phased array (SuperSonic Imagine, France) dedicated to transcranial human experiments and operating at 1 MHz. Experiments are conducted in phantom gels and ex vivo brain tissues through numerical phase aberrators. A motion-sensitized spin echo sequence (TE = 70 ms, TR = 1200 ms, spatial resolution is 2×2×7 mm3) is implemented to measure displacements induced by the acoustic radiation force of transmitted beams. Results: MR-ARFI allowed mapping the distribution of the radiation force at the focus of the array. After the recording of the MR phase signals for different US emissions, the proposed adaptive focusing technique was able to recover the spatial distribution of the phase aberrations. Total acquisition time for 384 ultrasonic emission channels was 2 hours. Conclusion: Those first results in clinical MR at 1.5 T show that adaptive focusing of a human transcranial brain HIFU system can be achieved within reasonable time under MR guidance for aberrator layers as strong as human skull. Ongoing work is aiming at accelerating the acquisition in order to reach acceptable durations for in vivo protocols.

MR‐Guided Ultrasonic Brain Therapy: High Frequency Approach

A novel MR-guided brain therapy device operating at 1MHz has been designed and constructed. The system has been installed and tested in a clinical 1.5 T Philips Achieva MRI. Three dimensional time domain finite differences simulations were used to compute the propagation of the wave field through three human skulls. The simulated phase distortions were used as inputs for transcranial correction and the corresponding pressure fields were scanned in the focal plane. At half of the maximum power (10 W/cm2 on the surface of the transducers), necroses were induced 2 cm deep in turkey breasts placed behind a human skull. In vitro experiments on human skulls show that simulations restore more than 85% of the pressure level through the skull bone when compared to a control correction performed with an implanted hydrophone. Finally, high power experiments are performed though the skull bone and a MR-Thermometry sequence is used to map the temperature rise in a brain phantom every 3 s in two orthogonal planes (focal plane and along the axis of the probe).

Reaching the optimal focusing and steering capabilities of transcranial HIFU arrays based on time reversal of acoustically induced cavitation bubble signature

Brain treatment with High Intensity Focused Ultrasound (HIFU) can be achieved by multichannel arrays through the skull using time-reversal focusing. Such a method requires a reference signal either sent by a real source embedded in brain tissues or computed from a virtual source, using the acoustic properties of the skull deduced from CT images. This non-invasive computational method allows precise focusing, but is time consuming and suffers from unavoidable modeling and repositioning errors which reduce the accessible acoustic pressure at the focus in comparison with real experimental time-reversal using an implanted hydrophone. Ex vivo simulations with a half skull immersed in a water tank allow us to reach at low amplitude levels a pressure ratio of 83% of the reference pressure (real time-reversal) at 1 MHz. Using this method to transcranially focus a pulse signal in an agar gel (model for in vivo bubble formation), we induced a cavitation bubble that generated an ultrasonic wave received by the array. Selecting the 1 MHz component, the signal was time reversed and re-emitted, allowing 97%plusmn1.1% of pressure ratio to be restored. To target points in the vicinity of the geometrical focus, conventional electronic steering from the reference signal has been achieved. Skull aberrations severely degrade the accessible pressure while moving away from the focus ( ~90% at 11 mm in the focal plane). Nevertheless, inducing cavitation bubbles close to the limit of the primary accessible zone allowed us to acquire multiple references signal to increase the electronic steering area by 50%.

MR-guided ultrasonic brain therapy: High frequency approach

A novel MR-guided brain therapy device operating at 1MHz has been designed and constructed. The system has been installed and tested in a clinical 1.5 T Philips Achieva MRI. Three dimensional time domain finite differences simulations were used to compute the propagation of the wave field through three human skulls. The simulated phase distortions were used as inputs for transcranial correction and the corresponding pressure fields were scanned in the focal plane. At half of the maximum power (10 W/cm2 on the surface of the transducers), necroses were induced 2 cm deep in turkey breasts placed behind a human skull. In vitro experiments on human skulls show that simulations restore more than 85% of the pressure level through the skull bone when compared to a control correction performed with an implanted hydrophone. Finally, high power experiments are performed though the skull bone and a MR-Thermometry sequence is used to map the temperature rise in a brain phantom every 3 s in two orthogonal planes (focal plane and along the axis of the probe).