Innovative aberration correction in ultrasound diagnostics with direct phase estimation for enhanced image quality

Leung S.A., Moore D., Gilbo Y., Snell J., Webb T.D., Meyer C.H., Miller G.W., Ghanouni P., Butts Pauly K.

Transcranial focused ultrasound with the InSightec Exablate system uses thermal ablation for the treatment of movement and mood disorders and blood brain barrier disruption for tumor therapy. The system uses computed tomography (CT) images to calculate phase corrections that account for aberrations caused by the human skull. This work investigates whether magnetic resonance (MR) images can be used as an alternative to CT images to calculate phase corrections. Phase corrections were calculated using the gold standard hydrophone method and the standard of care InSightec ray tracing method. MR binary image mask, MR-simulated-CT (MRsimCT), and CT images of three ex vivo human skulls were supplied as inputs to the InSightec ray tracing method. The degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. Targets at the geometric focus and 5 mm lateral to the geometric focus were investigated. There was no statistical difference between any of the metrics at either target using either MRsimCT or CT for phase aberration correction. As opposed to the MRsimCT, the use of CT images for aberration correction requires registration to the treatment day MR images; CT misregistration within a range of ± 2 degrees of rotation error along three dimensions was shown to reduce focal spot intensity by up to 9.4%. MRsimCT images used for phase aberration correction for the skull produce similar results as CT-based correction, while avoiding both CT to MR registration errors and unnecessary patient exposure to ionizing radiation.

Leonov D., Kodenko M., Leichenco D., Nasibullina A., Kulberg N.

Commercial medical ultrasound phantoms are highly specific as they simulate particular clinical scenarios. This makes them expensive to use in multi-target research and training. General approaches to human tissue and organ modeling are described in the manufacturing methodology, access to which is restricted by the manufacturer's trade secret. Our aim is to propose a reproducible methodology to design a head phantom for transcranial ultrasound training and research from widely available materials and to validate its applicability. To create an anthropomorphic phantom, we used data from real patients obtained by CT and MRI scans. We combined FDM and LCD 3D printing to achieve the desired acoustic performance and ergonomics of the phantom. We fabricated the phantom using polyvinyl chloride plastisol, photopolymer, and PLA to simulate brain tissue, temporal acoustic windows, and acoustically opaque parts of the skull, respectively. Notably, the phantom fabrication method uses only readily available materials and is easy to reproduce. We developed a basic one and anatomical one versions of the head phantom. The basic version contains a simplified brain: tissue-mimicking material is poured into the skull with needles inserted, which specific pattern is easy to recognize in B-mode images. The anatomical version has an anatomically correct brain dummy extracted from MRI data and contains multiple randomly distributed small metal, plastic, and bony objects ranging in size from 1 to 3 mm each. The proposed methodology allows producing head phantoms for transcranial ultrasound training and research. The anatomical accuracy of the model is proved by ultrasonography and CT studies. Both versions of the phantom comprise the skull and the brain and are intended for ultrasound imaging through the temporal bone acoustic window. Needles and small objects serve as navigation targets during the training procedure. The basic version helps learning basic navigation skills, while the anatomical one provides a realistic setting to perform the diagnostic procedure.

Leonov D.V., Kulberg N.S., Yakovleva T.V., Solovyova P.D.

The presence of cranial bones in the ultrasound propagation path seriously complicates the imaging of tissues and blood vessels of the brain since the bones distort the ultrasound field, introducing phase and amplitude aberrations. Such distortions are not always apparent since complete information about the studied object is fundamentally inaccessible. The article develops a new approach that uses the synthetic aperture method to detect wavefront aberrations. A quantitative parameter is proposed that characterizes the presence of aberrations by measuring the RMS width of the angular intensity distribution. Experimental results were obtained at a frequency of 2 MHz using phantom and in vivo transcranial data. It is shown that in the presence of aberrations, the value of the proposed parameter increases by 22–45% with respect to the theoretical value for the aberrationless case.

Osipov L.V., Kulberg N.S., Skosyrev S.V., Leonov D.V., Grigorev G.K., Vladzimirskiy A.V., Morozov S.P.

Ultrasound imaging through the intact skull is challenging because of the skull-induced aberrations and signal attenuation. We have designed an experimental ultrasound diagnostic system for noninvasive brain imaging through the intact skull. To overcome skull-induced aberrations and focus efficiently, the system implements the correction procedure based on a beacon approach. This approach is considered classical and highly accurate in comparison with other correction methods. Operation of the system requires two probes working at 3-4 MHz central frequency. The probes are attached coaxially on both sides of the head to the acoustic transparency windows.

Kim J., Kasoji S., Durham P.G., Dayton P.A.

Cavitation is an important phenomenon in biomedical acoustics. It can produce both desired outcomes (i.e., local therapeutic effects in vivo) and undesired outcomes (i.e., tissue damage), and it is, thus, important to both understand and direct cavitation fields. Through the use of three-dimensional-printed acoustic lenses and cavitation-sensitive acoustic phantoms, we demonstrate the generation of arbitrary shape two-dimensional (2D) microbubble cavitation fields. In this study, we demonstrate shaping a 1 MHz acoustic beam as the character “7” on a target plane that contains a higher mechanical index than the cavitation threshold for encapsulated microbubbles in a gelatin phantom. The lens pattern is first designed by calculating the phase map of the desired field using an angular spectrum approach. After lens implementation, acoustic pulsing through the lens generated the target acoustic field in a phantom and produced a cavitation map following the intended 2D pattern. The cavitation pattern was similar (with the structural similarity of 0.476) to the acoustic pressure map of the excitation beam.

Deng L., Hughes A., Hynynen K.

Objective: There may be a need to perform dynamic skull aberration corrections during the non-invasive high-intensity transcranial treatment with magnetic resonance imaging (MRI) -guided focused ultrasound in order to accurately and rapidly restore the focus in the brain. Methods: This could possibly be accomplished by using an ultrasound-based correction method based on the skulls' thickness resonance frequencies. The focus of a 500 kHz transducer was centered in the ex vivo human skull caps at different temperatures. The pulse-echoed signals reflected from the skulls were analyzed in the frequency domain to reveal the resonance frequencies for the phase shift calculation. The accuracy was compared to both hydrophone and computed tomography (CT) based analytical methods. Results: Around 73% of the measurements (n = 784) were in the optimal constructive interference region, with a 15° decrease in the average phase error compared to the previous study. In the best implementation, it performed approximately the same or better than the CT based analytical method currently in clinical use. Linear correlation was found between the resonance frequencies or skull induced phase shifts and the skull temperature with an average rate of -0.4 kHz/°C and 2.6 deg/°C, respectively. Conclusion: The ultrasound based resonance method has shown the feasibility of detecting heating-induced changes of skull phase shift non-invasively and accurately. Significance: Since the technique can be made MRI compatible and integrated in the therapy arrays, it may enable temperature tracking and adaptive focusing during high-intensity transcranial ultrasound treatments, to prevent skull overheating and preserve the transcranial focusing integrity.

Brown M.D., Cox B.T., Treeby B.E.

Acoustic holograms can be used to form complex distributions of pressure in 3D at MHz frequencies from simple inexpensive ultrasound sources. The generation of such fields is vital to a diverse range of applications in physical acoustics. However, at present, the application of acoustic holograms is severely hindered by the static nature of the resulting fields. In this work, it is shown that by intentionally reducing the diffraction efficiency of each hologram, it is possible to create stackable acoustic holograms that can be repositioned to reconfigure the combined acoustic field. An experimental test-case consisting of two holograms, each designed to generate a distinct distribution of acoustic foci, is used to demonstrate the feasibility of this approach. Field scans taken for four different positions of the two holograms confirm that the individual patterns for each hologram can be arbitrary translated relative to one another. This allows for the generation of a much greater range of fields from a single transducer than could be created using a single hologram.

Lambert W., Cobus L.A., Frappart T., Fink M., Aubry A.

Focusing waves inside inhomogeneous media is a fundamental problem for imaging. Spatial variations of wave velocity can strongly distort propagating wave fronts and degrade image quality. Adaptive focusing can compensate for such aberration but is only effective over a restricted field of view. Here, we introduce a full-field approach to wave imaging based on the concept of the distortion matrix. This operator essentially connects any focal point inside the medium with the distortion that a wave front, emitted from that point, experiences due to heterogeneities. A time-reversal analysis of the distortion matrix enables the estimation of the transmission matrix that links each sensor and image voxel. Phase aberrations can then be unscrambled for any point, providing a full-field image of the medium with diffraction-limited resolution. Importantly, this process is particularly efficient in random scattering media, where traditional approaches such as adaptive focusing fail. Here, we first present an experimental proof of concept on a tissue-mimicking phantom and then, apply the method to in vivo imaging of human soft tissues. While introduced here in the context of acoustics, this approach can also be extended to optical microscopy, radar, or seismic imaging.

Kyriakou A., Neufeld E., Werner B., Paulides M.M., Szekely G., Kuster N.

The development of phased array transducers and their integration with magnetic resonance (MR) guidance and thermal monitoring has established transcranial MR-guided focused ultrasound (tcMRgFUS) as an attractive non-invasive modality for neurosurgical interventions. The presence of the skull, however, compromises the efficiency of transcranial FUS (tcFUS) therapy, as its heterogeneous nature and acoustic characteristics induce significant phase aberrations and energy attenuation, especially at the higher acoustic frequencies employed in tcFUS thermal therapy. These aberrations may distort and shift the acoustic focus as well as induce heating at the patient's scalp and skull bone. Phased array transducers feature hundreds of elements that can be driven individually, each with its own phase and amplitude. This feature allows for compensation of skull-induced aberrations by calculation and application of appropriate phase and amplitude corrections. In this paper, we illustrate the importance of precise refocusing and provide a comprehensive review of the wide variety of numerical and experimental techniques that have been used to estimate these corrections.

Lindsey B.D., Smith S.W.

Having previously presented the ultrasound brain helmet, a system for simultaneous 3-D ultrasound imaging via both temporal bone acoustic windows, the scanning geometry of this system is utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals, followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3-D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e., several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing, or beacon, array, updates the transmit and receive delays of 5 isoplanatic patches within a 64° x 64° volume. In phantom experiments, color flow voxels above a common threshold have also increased by an average of 92%, whereas color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting that such a technique may be beneficial in the future for performing noninvasive 3-D color flow imaging of cerebrovascular disease, including stroke.

Tillett J.C., Astheimer J.P., Waag R.C.

Correction of aberration in ultrasound imaging uses the response of a point reflector or its equivalent to characterize the aberration. Because a point reflector is usually unavailable, its equivalent is obtained using statistical methods, such as processing reflections from multiple focal regions in a random medium. However, the validity of methods that use reflections from multiple points is limited to isoplanatic patches for which the aberration is essentially the same. In this study, aberration is modeled by an offset phase screen to relax the isoplanatic restriction. Methods are developed to determine the depth and phase of the screen and to use the model for compensation of aberration as the beam is steered. Use of the model to enhance the performance of the noted statistical estimation procedure is also described. Experimental results obtained with tissue-mimicking phantoms that implement different models and produce different amounts of aberration are presented to show the efficacy of these methods. The improvement in b-scan resolution realized with the model is illustrated. The results show that the isoplanatic patch assumption for estimation of aberration can be relaxed and that propagation-path characteristics and aberration estimation are closely related.

Vignon F., Shi W.T., Burcher M.R., Powers J.E.

Ammi A.Y., Mast T.D., Huang I.-., Abruzzo T.A., Coussios C., Shaw G.J., Holland C.K.

Adjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke. The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.03 and 2.00-MHz ultrasound transducers to identify optimal ultrasound parameters that would maximize penetration and minimize aberration of the beam. To achieve this goal, in vitro experiments were conducted on five human skull specimens. In a water-filled tank, two unfocused transducers (0.12 and 1.03 MHz) and one focused transducer (2.00 MHz) were consecutively placed near the right temporal bone of each skull. A hydrophone, mounted on a micropositioning system, was moved to an estimated location of the middle cerebral artery (MCA) origin, and measurements of the surrounding acoustic pressure field were performed. For each measurement, the distance from the position of maximum acoustic pressure to the estimated origin of the MCA inside the skulls was quantified. The -3 dB depth-of-field and beamwidth in the skull were also investigated as a function of the three frequencies. Results show that the transducer alignment relative to the skull is a significant determinant of the detailed behavior of the acoustic field inside the skull. For optimal penetration, insonation normal to the temporal bone was needed. The shape of the 0.12-MHz intracranial beam was more distorted than those at 1.03 and 2.00 MHz because of the large aperture and beamwidth. However, lower ultrasound pressure reduction was observed at 0.12 MHz (22.5%). At 1.03 and 2.00 MHz, two skulls had an insufficient temporal bone window and attenuated the beam severely (up to 96.6% pressure reduction). For all frequencies, constructive and destructive interference patterns were seen near the contralateral skull wall at various elevations. The 0.12-MHz ultrasound beam depth-of-field was affected the most when passing through the temporal bone and showed a decrease in size of more than 55% on average. The speed of sound in the temporal bone of each skull was estimated at 1.03 MHz and demonstrated a large range (1752.1 to 3285.3 m/s). Attenuation coefficients at 1.03 and 2.00 MHz were also derived for each of the five skull specimens. This work provides needed information on ultrasound beam shapes inside the human skull, which is a necessary first step for the development of an optimal transcranial ultrasound-enhanced thrombolysis device.

Jensen J.A., Nikolov S.I., Gammelmark K.L., Pedersen M.H.

The paper describes the use of synthetic aperture (SA) imaging in medical ultrasound . SA imaging is a radical break with today’s commercial systems, where the image is acquired sequentially one image line at a time. This puts a strict limit on the frame rate and the possibility of acquiring a sufficient amount of data for high precision flow estimation. These constrictions can be lifted by employing SA imaging. Here data is acquired simultaneously from all directions over a number of emissions, and the full image can be reconstructed from this data. The paper demonstrates the many benefits of SA imaging. Due to the complete data set, it is possible to have both dynamic transmit and receive focusing to improve contrast and resolution. It is also possible to improve penetration depth by employing codes during ultrasound transmission. Data sets for vector flow imaging can be acquired using short imaging sequences, whereby both the correct velocity magnitude and angle can be estimated. A number of examples of both phantom and in vivo SA images will be presented measured by the experimental ultrasound scanner RASMUS to demonstrate the many benefits of SA imaging.

Vignon F., Aubry J.F., Tanter M., Margoum A., Fink M.

Ultrasonic brain imaging remains difficult and limited because of the strong aberrating effects of the skull (absorption, diffusion and refraction of ultrasounds): high resolution transcranial imaging would require adaptive focusing techniques in order to correct the defocusing effect of the skull. In this paper, a noninvasive brain imaging device is presented. It is made of two identical linear arrays of 128 transducers located on each side of the skull. It is possible to separate the respective influence of the two bone windows on the path of an ultrasonic wave propagating from one array to the other, and thus estimate at each frequency the attenuation and phase shift locally induced by each bone window. The information obtained on attenuation and phase is used to correct the wave fronts that have to be sent through the skull in order to obtain a good focusing inside the skull. Compared to uncorrected wave fronts, the spatial shift of the focal spot is corrected, the width of the focal spot is reduced, and the sidelobes level is decreased up to 17dB. Transcranial images of a phantom are presented and exhibit the improvement in image quality provided by this new noninvasive adaptive focusing method.

Leonov D., Kulberg N., Yakovleva T.

AbstractBackgroundPreviously, there has been some work in the field of optical imaging on phase compensation by employing Legendre polynomials as an expansion of the phase function, and this seems to be an appealing unstudied area in the field of ultrasound imaging.PurposeThe paper is devoted to solving one of the problems of enhancing the authenticity of diagnostics data obtained in ultrasound visualization systems and presents a novel approach to aberration correction, which ensures a reliable eliminating of phase distortions. The novelty of the proposed approach consists in the use of the decomposition of the wave front by Legendre polynomials to approximate aberrations of the phase front of ultrasonic waves propagating through distorting layers.MethodsThe phase aberrations are corrected using a single sector probe that captures echoes in synthetic aperture mode. The proposed method approximates the changes in the wave front by means of the Legendre polynomials. The performance was investigated by placing a 13‐mm‐wide ultrasonic probe with 64 elements operating at 2 MHz on the surface of a commercial quality control phantom ATS Model 539 through a distorting layer. The following metrics were measured: peak value, root mean square (RMS), full width at half maximum (FWHM), contrast‐to‐noise ratio (CNR). During the experiments, three different aberrators were used interchangeably as distorting layers, two of which were made of photopolymer resin with RMS values of 39 and 97 ns and a speed of sound close to that of a human temporal bone tissue, and the third was an ex vivo human temporal bone with the RMS value of 44 ns. To test the correction, three regions inside the phantom were examined. Two‐sided nonparametric Wilcoxon rank‐sum test was used for assessing the statistical significance. The significance level for this study was set at α ≤ 0.05. To counteract the problem of multiple comparisons, the p‐values were adjusted by the Holm–Bonferroni correction method.ResultsThe statistically significant results have demonstrated the possibility of increasing peak intensity value up to 3.08 times, reducing the RMS width and FWHM of the intensity angular distribution down to 60% and 82%, respectively, and increasing CNR up to 2.12 times by using the proposed phase distortion correction method, compared with the case without correction. The results show that the method can be used as an effective aberration correction technique for all tested regions inside the phantom and distorting layers. Its usage allowed correcting up to 97% of the aberrations caused by the ex vivo temporal bone model.ConclusionThe results show that the usage of the proposed method for aberration correction can successfully increase the intensity and reduce the angular width of the ultrasound wave scattered by the point targets inside the phantoms. The method works with different distorting layers and is capable of correcting phase aberrations in multiple sections of the sonogram. The limitation of the proposed method consists in the fact that it requires the use of aperture synthesis and access to raw radiofrequency data, which restricts its application in common scanners.