Comparison between diffuse infrared and acoustic transmission over the human skull.

Skull-induced distortion and attenuation present a challenge to both transcranial imaging and therapy. Whereas therapeutic procedures have been successful in offsetting aberration using from prior CTs, this approach impractical for imaging. In effort to provide a simplified means for aberration correction, we have been investigating the use of diffuse infrared light as an indicator of acoustic properties. Infrared wavelengths were specifically selected for tissue penetration; however this preliminary study was performed through bone alone via a transmission mode to facilitate comparison with acoustic measurements. The inner surface of a half human skull, cut along the sagittal midline, was illuminated using an infrared heat lamp and images of the outer surface were acquired with an IR-sensitive camera. A range of source angles were acquired and averaged to eliminate source bias. Acoustic measurement were likewise obtained over the surface with a source (1MHz, 12.7mm-diam) oriented parallel to the skull surface and hydrophone receiver (1mm PVDF). Preliminary results reveal a positive correlation between sound speed and optical intensity, whereas poor correlation is observed between acoustic amplitude and optical intensity.

The feasibility of non-contact ultrasound for medical imaging.

High intensity focused ultrasound in air may provide a means for medical and biological imaging without direct coupling of an ultrasound probe. In this study, an approach based on highly focused ultrasound in air is described and the feasibility of the technique is assessed. The overall method is based on the observations that (1) ultrasound in air has superior focusing ability and stronger nonlinear harmonic generation as compared to tissue propagation and (2) a tightly focused field directed into tissue causes point-like spreading that may be regarded as a source for generalized diffraction tomography. Simulations of a spherically-curved transducer are performed, where the transducer's radiation pattern is directed from air into tissue. It is predicted that a focal pressure of 162 dB (2.5 kPa) is sufficient to direct ultrasound through the body, and provide a small but measurable signal (∼1 mPa) upon exit. Based on the simulations, a 20 cm diameter array consisting of 298 transducers is constructed. For this feasibility study, a 40 kHz resonance frequency is selected based on the commercial availability of such transducers. The array is used to focus through water and acrylic phantoms, and the time history of the exiting signal is evaluated. Sufficient data are acquired to demonstrate a low-resolution tomographic reconstruction. Finally, to demonstrate the feasibility to record a signal in vivo, a 75 mm × 55 mm section of a human hand is imaged in a C-mode configuration.

Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion.

Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

Longitudinal and shear mode ultrasound propagation in human skull bone.

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.

Local frequency dependence in transcranial ultrasound transmission.

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

Ultrasound phase-contrast transmission imaging of localized thermal variation and the identification of fat/tissue boundaries.

We present a new ultrasound technique for registering localized temperature changes in soft tissues. Conversely, small temperature changes may be induced in order to image tissue layers. The concept is motivated by the search for a compact, low cost method for guiding noninvasive thermal therapies; however its utility may extend to a wide range of imaging problems such as tumour imaging in the breast. This method combines ultrasound transmission imaging, planar projection techniques and phase-contrast theory. After outlining the theoretical foundation of the technique, its feasibility is tested by simulating localized heating within homogeneous tissue layers. Success of this imaging method is evaluated as a function of the ultrasound-imaging wavelength for a Gaussian-shaped heated region over the frequency range from 0.1 to 2 MHz. Furthermore we simulate two-dimensional image reconstruction from a receiving array. We conclude that thermal phase-contrast imaging in tissues is plausible for detecting the treatment spot in thermal therapies while operating at frequencies below 1 MHz. Additionally, it may also be possible to use the method for noninvasive thermometry. However, thermometry would require operation at higher frequencies at the tradeoff of increased attenuation and higher sensitivity to scattering, which needs to be further explored.

Superresolution ultrasound imaging using back-projected reconstruction.

An ultrasound technique for imaging objects significantly smaller than the source wavelength is investigated. Signals from a focused beam are recorded over an image plane in the acoustic farfield and backprojected in the wave-vector domain to the focal plane. A superresolution image recovery method is then used to analyze the Fourier spatial frequency spectrum of the signal in an attempt to deduce the location and size of objects in this plane. The physical foundation for the method is rooted in the fact that high spatial frequencies introduced by the object in fact affect the lower (nonevanescent) spatial frequencies of the overall signal. The technique achieves this by using a priori measurements of the ultrasound focus in water, which gives full spectral information about the image source. A guess is then made regarding the size and location of the object that distorted the field, and this is convolved with the a priori measurement, thus creating a candidate image. A large number of candidates are generated and the one whose spectrum best matches the uncorrected image is accepted. The method is demonstrated using 0.34- and 0.60-mm wires with a focused 1.05-MHz ultrasound signal and then a human hair (approximately 0.03 mm) with a 4.7-MHz signal.

Perspectives in clinical uses of high-intensity focused ultrasound.

Focused ultrasound holds promise in a large number of therapeutic applications. It has long been known that high intensity focused ultrasound can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible, with the development of high power ultrasound phased arrays and noninvasive monitoring methods. These technologies, combined with more sophisticated treatment planning methods allow noninvasive focusing in areas such as the brain, that were once thought to be unreachable. Meanwhile, exciting investigations are underway in microbubble-enhanced heating which could significantly reduce treatment times. These developments have promoted an increase in the number of potential applications by providing valuable new tools for medical research. This paper provides an overview of the scientific and engineering advances that are allowing the growth in clinical focused ultrasound applications. It also discusses some of these prospective applications, including the treatment of brain disorders and targeted drug delivery.

Enhanced ultrasound transmission through the human skull using shear mode conversion.

A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snell's critical angle experience a mode conversion from an incident longitudinal wave into a shear wave in the bone layers and then back to a longitudinal wave in the brain. The skull's shear speed provides a better impedance match, less refraction, and less phase alteration than its longitudinal counterpart. Therefore, the idea of utilizing a shear wave for focusing ultrasound in the brain is examined. Demonstrations of the phenomena, and numerical predictions are first studied with plastic phantoms and then using an ex vivo human skull. It is shown that at a frequency of 0.74 MHz the transskull shear method produces an amplitude on the order of--and sometimes higher than--longitudinal propagation. Furthermore, since the shear wave experiences a reduced overall phase shift, this indicates that it is plausible for an existing noninvasive transskull focusing method [Clement, Phys. Med. Biol. 47(8), 1219-1236 (2002)] to be simplified and extended to a larger region in the brain.

Preliminary results using ultrasound transmission for image-guided thermal therapy.

The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R(2)) of 0.6694 and bovine fat resulted in an R(2) of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R(2) of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery.

Correlation of ultrasound phase with physical skull properties.

Noninvasive treatment of brain disorders using focused ultrasound (US) requires a reliable model for predicting the distortion of the field due to the skull using physical parameters obtained in vivo. Previous studies indicate that control of US phase alone is sufficient for producing a focus through the skull using a phased US array. The present study concentrates on identifying methods to estimate phase distortion. This will be critical for the future clinical use of noninvasive brain therapy. Ten ex vivo human calvaria were examined. Each sample was imaged in water using computerized tomography (CT). The information was used to determine the inner and outer skull surfaces, thickness as a function of position, and internal structure. Phase measurement over a series of points was obtained by placing a skull fragment between a transducer and a receiver with the skull normal to the transducer. Correlation was found between the skull thickness and the US phase shift. A linear fit of the data follows that predicted by a homogeneous skull when average speed of sound 2650 m/s was used. Large variance (SD = 60 degrees, mean = 50 degrees ) indicates the additional role of internal bone speed and density fluctuations. In an attempt to reduce the variance, the skull was first studied as a three-layer structure. Next, density-dependent bone speed fluctuation was introduced to both the single-layer and three-layer models. It was determined that adjustment of the mean propagation speeds using density improves the overall phase prediction. Results demonstrate that it is possible to use thickness and density information from CT images to predict the US phase distortion induced by the skull accurately enough for therapeutic aberration correction. In addition, the measurements provide coefficients for phase dependence on skull thickness and density that can be used in clinical treatments.

A non-invasive method for focusing ultrasound through the human skull.

A technique for focusing ultrasound through the human skull is described and verified. The approach is based on a layered wavevector-frequency domain model, which propagates ultrasound from a hemisphere-shaped transducer through the skull using input from CT scans of the head. The algorithm calculates the driving phase of each transducer element in order to maximize the signal at the intended focus. This approach is tested on ten ex vivo human skulls using a 0.74 MHz, 320-element array. A stereotaxic reference frame is affixed to the skulls in order to provide accurate registration between the CT images and the transducer. The focal quality is assessed with a hydrophone placed inside the skull. In each trial the phase correction algorithm successfully restored the focus inside the skull at a location within 1 mm from the intended focal point. The results demonstrate the feasibility of using the method for completely non-invasive ultrasound brain surgery and therapy.

The role of internal reflection in transskull phase distortion.

Phase distortion due to reflection in transcranial ultrasound propagation is investigated. Understanding of these phase-dependent properties is motivated by efforts to construct a reliable prediction model for noninvasive ultrasound therapy in the brain. The present study measures the phase of an ultrasound wave after propagation through an ex vivo human skull and considers the dependence of this phase on reflections between the transducer and the skull surface in addition to reflections within the skull. Experiments are performed using a human calvarium fragment placed between an underwater ultrasonic transducer and a polyvinylidene difluoride hydrophone. Data are presented indicating the ultrasound phase dependence as a function of burst length and the distance of the transducer element from the skull at a driving frequency of 0.5 MHz. Experimental results are compared with predictions obtained from a propagation model which considers transmission at the skull interfaces as well as multiple reflections within the skull. It is concluded that by using short ultrasound bursts a distance may be indicated that beyond which the contributions of transducer reflections on the phase of the propagating wave may be neglected. Additionally, a comparison of the measurements with simulated data supports the contention that for reasonably small incident angles, reflection within the skull causes minimal phase shift.

A hemisphere array for non-invasive ultrasound brain therapy and surgery.

Ultrasound phased arrays may offer a method for non-invasive deep brain surgery through the skull. In this study a hemispherical phased array system is developed to test the feasibility of trans-skull surgery. The hemispherical shape is incorporated to maximize the penetration area on the skull surface, thus minimizing unwanted heating. Simulations of a 15 cm radius hemisphere divided into 11, 64, 228 and 512 elements are presented. It is determined that 64 elements are sufficient for correcting scattering and reflection caused by trans-skull propagation. An optimal operating frequency near 0.7 MHz is chosen for the array from numerical and experimental thermal gain measurements comparing the power between the transducer focus and the skull surface. A 0.665 MHz air-backed PZT array is constructed and evaluated. The array is used to focus ultrasound through an ex vivo human skull and the resulting fields are measured before and after phase correction of the transducer elements. Finally, to demonstrate the feasibility of trans-skull therapy, thermally induced lesions are produced through a human skull in fresh tissue placed at the ultrasound focus inside the skull.

Investigation of a large-area phased array for focused ultrasound surgery through the skull.

Non-invasive treatment of brain disorders using ultrasound would require a transducer array that can propagate ultrasound through the skull and still produce sufficient acoustic pressure at a specific location within the brain. Additionally, the array must not cause excessive heating near the skull or in other regions of the brain. A hemisphere-shaped transducer is proposed which disperses the ultrasound over a large region of the skull. The large surface area covered allows maximum ultrasound gain while minimizing undesired heating. To test the feasibility of the transducer two virtual arrays are simulated by superposition of multiple measurements from an 11-element and a 40-element spherically concave test array. Each array is focused through an ex vivo human skull at four separate locations around the skull surface. The resultant ultrasound field is calculated by combining measurements taken with a polyvinylidene difluoride needle hydrophone providing the fields from a 44-element and a 160-element virtual array covering 88% and 33% of a hemisphere respectively. Measurements are repeated after the phase of each array element is adjusted to maximize the constructive interference at the transducer's geometric focus. An investigation of mechanical and electronic beam steering through the skull is also performed with the 160-element virtual array, phasing it such that the focus of the transducer is located 14 mm from the geometric centre. Results indicate the feasibility of focusing and beam steering through the skull using an array spread over a large surface area. Further, it is demonstrated that beam steering through the skull is plausible.

Absolute measurements of ultrasonic pressure by using high magnetic fields.

A hydrophone is introduced that exploits the emf signal generated in a conductor when sonicated in the presence of a uniform static magnetic field. The method uses a small metal coil or metal membrane as a hydrophone receiver. Acoustic signals at 748 kHz are introduced in 1.5 T and 4.7 T fields and recorded both through direct electrical contact with the hydrophone and via RF pick-up coils, allowing wireless placement of the hydrophone. Linear response Is confirmed over four orders of magnitude in the pressure amplitude. Waveforms determined from the detected voltage are shown to be in excellent agreement with those obtained using a calibrated polyvinylidene difluoride film, and absolute values correlate within 20%. The methods are conceptually suitable for use in the presence of the high and uniform field of commercial MR scanners. The hydrophone may appear particularly useful as a quality assurance device in therapeutic and diagnostic acoustic techniques that use MRI.