Transcranial Focusing Research Articles

Transcranial focused ultrasound with multielement arrays: Decreasing the number of transducers without compromising the focusing quality

Transcranial ultrasonic brain therapy at frequencies higher than 500 kHz requires adaptive focusing to compensate for the aberrations induced by the skull bone. This can be achieved by using multi-element arrays driven by a dedicated electronics. A growing number of elements was used to improve the focusing: 64 elements in 2000 [1], 300 in 2003 [2], 1024 in 2013 [3], and more to come. We will present some of the salient results obtained pre-clinically and clinically with such multi-element transcranial devices. Nevertheless, we will show that comparable transcranial focusing can be achieved with a novel approach in rupture with the current trend. It consists in a single-element transducer covered with a 3D silicone acoustic lens of variable and controlled thickness. Similar lenses have been introduced in the past to perform multiple focusing patterns in homogenous media [4] but recent 3d printing capabilities make 3D lenses a feasible option for transcranial adaptive focusing. We will show that the use of a lenses increases the acoustic intensity by 97 ± 56% on average, on three human skulls. [1] G. Clement et al., “A hemisphere array for non-invasive ultrasound brain therapy and surgery,” Phys. Med. Biol. 2000. [2] M. Pernot et al., “High power transcranial beam steering for ultrasonic brain therapy,” Phys. Med. Biol. 2003. [3] N. Lipsman et al., “MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study,” The Lancet Neurology 2013. [4] T. Fjield et al., “Low-profile lenses for ultrasound surgery,” Phys. Med. Biol. 1999.

Focusing ultrasound through bones: Past, current, and future transcostal and transskull strategies

Bones reflect, refract, distort, and absorb ultrasonic waves. Most medical application of ultrasound avoid bony structures. Nevertheless, for liver and brain therapy, the rib cage and the skull are in the ultrasonic path. We will present non-invasive methods to detect the presence of the ribs and shape the beam in order to sonicate in between the ribs. It is thus possible to non-invasively aim a target shadowed by the rib cage while avoiding sonication through the bones. Such approaches take advantage of the ultrasonic imaging capabilities of multi-element arrays. Nevertheless, non-invasive brain therapy requires to sonicate through the skull. CT and MR- based techniques have been developed to estimate the phase shifts induced by the skull. Dedicated multi-element arrays have been developed to generate the appropriate phase-corrected signals. The number of elements of the arrays has progressively increased in order to shape at best the corrected beam (64 elements in 2000, 300 in 2003, and 1024 in 2012): clinical transcranial therapies will be presented for the treatment of essential tremor, parkinsonian tremors, and tumors with a 1024 element array. We will also present preliminary results of a novel game changing transcranial focusing technique requiring a dramatically lower number of elements.

Accurate simulation of transcranial ultrasound propagation for ultrasonic neuromodulation and stimulation.

Non-invasive, focal neurostimulation with ultrasound is a potentially powerful neuroscientific tool that requires effective transcranial focusing of ultrasound to develop. Time-reversal (TR) focusing using numerical simulations of transcranial ultrasound propagation can correct for the effect of the skull, but relies on accurate simulations. Here, focusing requirements for ultrasonic neurostimulation are established through a review of previously employed ultrasonic parameters, and consideration of deep brain targets. The specific limitations of finite-difference time domain (FDTD) and k-space corrected pseudospectral time domain (PSTD) schemes are tested numerically to establish the spatial points per wavelength and temporal points per period needed to achieve the desired accuracy while minimizing the computational burden. These criteria are confirmed through convergence testing of a fully simulated TR protocol using a virtual skull. The k-space PSTD scheme performed as well as, or better than, the widely used FDTD scheme across all individual error tests and in the convergence of large scale models, recommending it for use in simulated TR. Staircasing was shown to be the most serious source of error. Convergence testing indicated that higher sampling is required to achieve fine control of the pressure amplitude at the target than is needed for accurate spatial targeting.

Investigation of the correlation between diffuse infrared and ultrasound for transcranial ultrasound

Over the past two decades the feasibility for using transcranial ultrasound as both a therapeutic and diagnostic tool has been established. Various aberration-correction techniques have been proposed to achieve transcranial focusing, including computed tomography-derived model based corrections, ultrasound-derived model based corrections, magnetic resonance acoustic radiation force techniques, and techniques involving the invasive introduction of an acoustic source or receiver into the brain. Here, we investigate the correlation between transcranial infrared light (IR) and transcranial ultrasound, where we examine whether IR could be an indicator of any of the key acoustic properties that affect transcranial transmission (signal attenuation, speed of sound, and bone density). Nine human skull samples were utilized in the study. The interior of each sample was illuminated over its inner surface using a diffuse light source. Light transmitted to the outer surface was detected by a 3 mm diameter 940 nm infrared sensor. Acoustic measurements were likewise obtained in a water tank using a 12.7 mm diameter 1 MHz source and a needle hydrophone receiver. Results reveal a positive correlation between the acoustic time-of-flight and optical intensity (the correlation coefficient is between 0.5 and 0.9). Subsequent investigation shows this correlation to hold independent of the presence or absence of dura mater on the samples. Poor correlation is observed between acoustic amplitude and optical intensity (the correlation coefficient is between 0.1 and 0.7).

Modulation of transcranial focusing thermal deposition in nonlinear HIFU brain surgery by numerical simulation

As the skull induces strong aberrations in phase and amplitude during transcranial treatment of brain surgery, high-intensity focused ultrasound suffers degradation in beam shape and deposits significant heat in the skull which may cause thermal damage to the bone and surrounding tissue. The goal of this study is to optimize the transcranial pressure and thermal fields to reduce thermal damage to the skull and simultaneously concentrate more energy in the focal region and make its size controllable during transcranial brain tumor treatment by modulating the excitation signals of the transducer array (including the phase and amplitude) and superposing the signals used to reduce peak pressure in the skull. A 3D numerical model was developed based on the reconstructed images from high-resolution CT scans of a human skull and a 64-element phased array to simulate acoustic propagation and thermal behavior calculated by the finite-difference time domain method. The simulation showed that more energy was focused at the setting target with little temperature elevation in the skull after correcting phase and amplitude and reducing peak pressure in the skull; through modulating the input intensity of arrays, the volume of focal regions located off-axis could be made equal to the volume achieved with on-axis focusing.

On the use of fast marching methods for transcranial beam focusing

In this talk, we will present our recent studies on the use of fast marching methods for transcranial beam focusing. Three topics will be included: beam focusing for transcranial B-mode imaging, beam focusing for transcranial photoacoustic tomography, and beam focusing of a spherical array for therapy. To correct for the phase aberration from the skull, two critical steps are needed prior to brain imaging or treatment. In the first step, the skull shape and speed of sound are acquired by either CT scans or ultrasound scans. In the second step, fast marching methods are used to compute the phase delay based on the known skull shape and sound speed from the first step, and the computation can be completed in seconds even for 3D problems. The computed phase delays are then used in combination with the conventional delay-and-sum algorithm for generating images. They can also be readily used for transcranial beam focusing for therapeutic purposes. Numerical simulation results will be presented to show the robustness of fast marching methods.

Direct phase projection and transcranial focusing of ultrasound for brain therapy

Ultrasound can be used to noninvasively treat the human brain with hyperthermia by focusing through the skull. To obtain an accurate focus, especially at high frequencies (>500 kHz), the phase of the transmitted wave must be modified to correct the aberrations introduced by the patient's individual skull morphology. Currently, three-dimensional finite-difference time-domain simulations are used to model a point source at the target. The outward-propagating wave crosses the measured representation of the human skull and is recorded at the therapy array transducer locations. The signal is then time reversed and experimentally transmitted back to its origin. These simulations are resource intensive and add a significant delay to treatment planning. Ray propagation is computationally efficient because it neglects diffraction and only describes two propagation parameters: the wave's direction and the phase. We propose a minimal method that is based only on the phase. The phase information is projected from the external skull surface to the array locations. This replaces computationally expensive finite-difference computations with an almost instantaneous direct phase projection calculation. For the five human skull samples considered, the phase distribution outside of the skull is shown to vary by less than λ/20 as it propagates over a 5 cm distance and the validity of phase projection is established over these propagation distances. The phase aberration introduced by the skull is characterized and is shown to have a good correspondence with skull morphology. The shape of this aberration is shown to have little variation with propagation distance. The focusing quality with the proposed phase-projection algorithm is shown to be indistinguishable from the gold-standard full finite-difference simulation. In conclusion, a spherical wave that is aberrated by the skull has a phase propagation that can be accurately described as radial, even after it has been distorted. By combining finite-difference simulations with a phase-projection algorithm, the time required for treatment planning is significantly reduced. The correlation length of the phase is used to validate the algorithm and it can also be used to provide guiding parameters for clinical array transducer design in terms of transducer spacing and phase error.

Applications of Transcranial Focused Ultrasound Surgery

Applications of Transcranial Focused Ultrasound Surgery

Ultrasound focusing using magnetic resonance acoustic radiation force imaging: Application to ultrasound transcranial therapy

Magnetic resonance guided ultrasonic therapy is a promising minimally invasive technology for constantly growing variety of clinical applications. Delivery of focused ultrasound (FUS) energy to the targeted point with optimal intensity is highly desired; however, due to tissue aberrations, optimal focal intensity is not always achieved. Especially in transcranial applications, the acoustic waves are shifted and distorted mainly by the skull. In order to verify that magnetic resonance acoustic radiation force imaging (MR-ARFI) can be used as a focusing tool in transcranial treatments, such an imaging was applied in vivo on a porcine brain via ex vivo human skull. Then, by the use of MR-ARFI technique, an improved ultrasound focusing algorithm is proposed and demonstrated for both transcranial and none brain applications. MR-ARFI images were acquired on a GE 1.5 T scanner equipped with InSightec FUS systems ExAblate 2000 and ExAblate 4000. Imaging was performed with MR-ARFI sequences of line-scan spin-echo and single-shot gradient-echo echo-planar. The in-plane resolution of both acquisitions was 0.9 x 0.9 mm2. The total acquisition time of MR-ARFI image was 31 s by the line-scan sequence and 1 s by the echo-planar sequence. An in vivo experiment was performed using FUS transducer, which is built out of 1024 ultrasound transmitting piezoelectric elements at 220 kHz frequency. The transducer was focused into the brain of a pig, which was wrapped in a human skull, in degassed water environment to resemble human treatments. The pig underwent a wide bilateral craniectomy to prevent a bone heating from the ultrasound beams. Two focusing experiments were performed in phantoms using 1 MHz and 710 kHz FUS transducers working with 208 and 225 elements, respectively. In the first experiment, aberration was added virtually to the apparatus by adding random phases to the phase map of the transducer. A simple focusing correction scheme was used, in which the corrected phase of a group of elements was chosen such that it maximizes the radiation force at the focal point. In the second experiment, aberrations made by a human skull were corrected using geometrical and phase based adjustments on segments of the transducer. A maximum displacement of 10 microm was obtained using 1.4 kW acoustic power on a live pig's head that its skull was removed and replaced by ex vivo human skull. Aberration correction using MR-ARFI resulted in near optimal focus, as the radiation force was similar to the nonaberration case. Transcranial, MR-ARFI based aberration correction performed better than CT based aberration correction, a technique that is currently used in brain FUS treatments. In the present work, the authors show for the first time a result of MR-ARFI in a live brain through ex vivo human skull. They have demonstrated that aberration correction could be done using MR-ARFI by measuring the radiation force at the focal point. Aberration correction using MR-ARFI is a promising noninvasive technique for transcranial focusing, which may result in near optimal focus and more reliable and safer brain FUS treatments.

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.

Adaptive focusing for bone and motion artifacts corrections in High Intensity Focused Ultrasound Therapy

Despite extensive and fast progress of HIFU clinical applications, many issues still need to be addressed. Distortions caused by defocusing obstacles, such as the skull or ribs, on the ultrasonic therapeutic beam are still being investigated. Multi-element transducer technology must be used in order to achieve such transcranial or transcostal adaptive focusing. Second, the problem of motion artifacts, a key component in the treatment of abdominal lesions, has been shown to significantly influence the efficacy and treatment time. Though many methods have been proposed for the detection of organ motion, little work has been done to develop a comprehensive solution including motion tracking and feedback correction in real time. This paper is a review of the work achieved by authors in transcranial HIFU, transcostal HIFU, and motion compensated HIFU. For these three issues, the optimal solution can be reached using the same technology of multi-element transducers devices able to work both in Transmit and Receive modes.

Treatment of near-skull brain tissue with a focused device using shear-mode conversion: a numerical study

Shear mode transmission through the skull has been previously proposed as a new trans-skull propagation technique for noninvasive therapeutic ultrasound (Clement 2004 J. Acoust. Soc. Am. 115 1356–64). The main advantage of choosing shear over longitudinal mode resides on the fact that there is less wavefront distortion with the former. In the present study, the regions of the brain suitable for shear-mode transmission were established for a simple focused ultrasound device. The device consists of a spherically curved transducer that has a focal length of 10 cm, an aperture between 30° and 60° and operates at 0.74 MHz. The regions suitable for shear-mode transmission were determined by the shear wave acoustic windows that matched the shape of the device acoustic field. The acoustic windows were calculated using segmentation and triangulation of outer and inner faces of skull from 3D-MRI head datasets. Nine heads of healthy adults were analyzed. The surface considered for the calculations was the head region found above the supra-orbital margin. For every inspected point in the brain volume, the axis of the device was determined by the vector between this inspection point and a point located in the center of the brain. Numerical predictions of the acoustic field, where shear-mode conversion through the skull was considered, were obtained and compared to the case of water-only conditions. The brain tissue that is close to the skull showed suitable acoustic windows for shear waves. The central region of the brain seems to be unreachable using shear-mode. Analysis of the acoustic fields showed a proportional relation between the acoustic window for shear mode and the effective degree of focusing. However, this relation showed significant differences among specimens. In general, highly focused fields were obtained when the acoustic window for shear waves (ASW) intersected more than 67% of the entering acoustic window (ATX) of the device. The average depth from the inner surface of the skull showing this intersection value was 13 ± 10 mm (mean ± SD). The differences of the degree of focusing observed among patients suggest that the intersection ASW∩ATX can be used as a preliminary criterion for screening and calculation of the acoustic fields should confirm the degree of focusing patient by patient. In conclusion, shear waves provide a useful method for trans-cranial focusing in regions close to the skull surface.

Compensating for bone interfaces and respiratory motion in high-intensity focused ultrasound

Bursts of focused ultrasound energy a thousand times more intense than diagnostic ultrasound have become a non-invasive option for treating cancer, from breast to prostate or uterine fibroid, during the last decade. Despite this progress, many issues still need to be addressed. First, the distortions caused by defocusing obstacles, such as the skull or ribs, on the ultrasonic therapeutic beam are still being investigated. Multi-element transducer technology must be used in order to achieve such transcranial or transcostal adaptive focusing. Second, the problem of motion artifacts, a key component in the treatment of abdominal lesions, has been shown significantly to influence the efficacy and treatment time. Though many methods have been proposed for the detection of organ motion, little work has been done to develop a comprehensive solution including motion tracking and feedback correction in real time. This paper is a review of the work achieved by authors in transcranial high-intensity focused ultrasound (HIFU), transcostal HIFU and motion compensated HIFU. For these three issues, the optimal solution can be reached using the same technology of multi-element transducers devices able to work both in transmit and receive modes.

A numerical study of transcranial focused ultrasound beam propagation at low frequency

The feasibility of transcranial ultrasound focusing with a non-moving phased array and without skull-specific aberration correction was investigated using computer simulations. Three cadaver skull CT image data sets were incorporated into an acoustic wave transmission model to simulate transskull ultrasound wave propagation. Using a 0.25 MHz hemispherical array (125 mm radius of curvature, 250 mm diameter, 24 255 elements), the simulated beams could be focused and steered with transducer element driving phases and amplitude adjusted for focal beam steering in water (water-path). A total of 82 foci, spanning wide ranges of distance in the three orthogonal dimensions, were simulated to test the focal beam steering capability inside the three skulls. The acoustic pressure distribution in a volume of 20 × 20 × 20 mm3 centred at each focus was calculated with a 0.5 mm spacing in each axis. Clearly defined foci were retained through the skulls (skull-path) in most cases. The skull-path foci were on average 1.6 ± 0.8 mm shifted from their intended locations. The −3 dB skull-path beam width and length were on average 4.3 ± 1.0 mm and 7.7 ± 1.8 mm, respectively. The skull-path sidelobe levels ranged from 25% to 55% of the peak pressure values. The skull-path peak pressure levels were about 10%–40% of their water-path counterparts. Focusing low-frequency beam through skull without skull-specific aberration correction is possible. This method may be useful for applying ultrasound to disrupt the blood–brain barrier for targeted delivery of therapeutic or diagnostic agents, or to induce microbubbles, or for other uses of ultrasound in brain where the required power levels are low and the sharp focusing is not needed.