Claudio Simon

Two-dimensional temperature estimation using diagnostic ultrasound

A two-dimensional temperature estimation method was developed based on the detection of shifts in echo location of backscattered ultrasound from a region of tissue undergoing thermal therapy. The echo shifts are due to the combination of the local temperature dependence of speed of sound and thermal expansion in the heated region. A linear relationship between these shifts and the underlying tissue temperature rise is derived from first principles and experimentally validated. The echo shifts are estimated from the correlation of successive backscattered ultrasound frames, and the axial derivative of the accumulated echo shifts is shown to be proportional to the temperature rise. Sharp lateral gradients in the temperature distribution introduce ripple on the estimates of the echo shifts due to a thermo-acoustic lens effect. This ripple can be effectively reduced by filtering the echo shifts along the axial and lateral directions upon differentiation. However, this is achieved at the expense of spatial resolution. Experimental evaluation of the accuracy (0.5/spl deg/C) and spatial resolution (2 mm) of the algorithm in tissue mimicking phantoms was conducted using a diagnostic ultrasound imaging scanner and a therapeutic ultrasound unit. The estimated temperature maps were overlaid on the gray-scale ultrasound images to illustrate the applicability of this technique for image guidance of focused ultrasound thermal therapy.

High intensity focused ultrasound effect on cardiac tissues: potential for clinical application.

High intensity focused ultrasound (HIFU) is an evolving technology with potential therapeutic applications. Utilizing frequencies of 500 kHz to 10 MHz, HIFU causes localized hyperthermia at predictable depths without injuring intervening tissue. Applications in neurosurgery, urology, oncology and, more recently, cardiology for selective cardiac conduction tissue ablation have been promising. A ‘noninvasive’ technique for causing localized tissue damage to relieve hemodynamic and life‐threatening obstruction in patients with congenital cardiac anomalies could replace more invasive procedures. We, therefore, investigated the ability of HIFU to create lesions in mammalian cardiac tissues ex vivo. Porcine valve leaflet, canine pericardium, human newborn atrial septum, and right atrial appendage were studied. Specimens were mounted and immersed in a water bath at room temperature. Using a 1‐MHz phased array transducer, ultrasound energy was applied with an acoustic intensity of 1630 W/cm2 or 2547 W/cm2 until a visible defect was created (duration 3 to 25 sec). Macroscopic and microscopic examination demonstrated precise defects ranging from 3 to 4 mm in diameter. No damage was identified to the surrounding tissues. Our study concluded that HIFU can create precise defects in different cardiac tissue without damage to the surrounding tissue. Further investigation is needed to assess potential clinical uses of this technology.

A robust and computationally efficient algorithm for mean scatterer spacing estimation

Mean scatterer spacing (MSS) has been recognized to be a useful tool for tissue characterization. Most of the work in this area either uses the amplitude or the phase information of the spectrum of the backscattered ultrasound echo to estimate the MSS. Simulations have shown that the latter approach is more robust in the presence of irregularities in the scatterer distribution. However, most of the algorithms based on the phase information of the spectrum are computationally demanding and cannot be used in real-time. We present a computationally efficient and robust algorithm which uses the magnitude and phase information of the spectrum to estimate the MSS. This algorithm exploits the spectral redundancy present in the backscattered echo signal by generating spectral lines through a nonlinear (quadratic) transformation of the RF echo signal. Results of simulations comparing the performance of the proposed algorithm and previous approaches from the literature are presented to demonstrate the robustness of the proposed algorithm. Experiments involving phantoms and in vitro tissue samples are also presented. The feasibility of implementing a real-time MSS imaging system based on the proposed method is discussed.

Image-guided noninvasive surgery with ultrasound phased arrays

The current status and the future needs of image-guided ultrasound phased array systems for noninvasive surgery are addressed. Preliminary results from an integrated image- guided therapeutic phased array system for noninvasive surgical applications currently being developed at our laboratory are shown. The therapeutic array utilizes piezo- composite transducer technology and operates (therapeutically) at 1 and 2 MHz. It consists of 64 elements on a spherical shell with a geometric center at 100 mm from its apex. The array was shown to be capable of producing well defined thermal lesions in tissue media at depths from 40 to 60 mm and to scan therapeutic foci up to +/- 15 mm from its geometric center. Image guidance is provided by a modified diagnostic ultrasound scanner which, in addition to providing standard B-scan images of the target region, provides real-time images of the temperature rise due to the therapeutic beam. The temperature information is obtained using a correlation based algorithm for echo displacement estimation, which can be directly related to local variation in tissue temperature due to the therapeutic beam. A complete description of the combined imaging/therapy system is given. Furthermore, illustrative examples of noninvasive real-time image-guided tissue ablation, temperature estimation, and temperature control are presented and discussed.

Motion compensation algorithm for noninvasive two-dimensional temperature estimation using diagnostic pulse-echo ultrasound

The feasibility of real-time non-invasive spatio-temporal temperature estimation from pulse-echo diagnostic ultrasound data has been previously demonstrated in stationary phantoms. The method is based on first estimating the axial shifts of the RF-echo data due to local changes in the speed of sound and thermal expansion in the propagating medium, and then differentiating these estimates along axial direction to obtain the temperature rise map. In a clinical setup, however, translation, rotation and deformation affect the estimates. In this paper we introduce an algorithm to compensate for tissue translation and uniform deformation along the axial and lateral directions of the ultrasound imaging plane. This is achieved by separating the components of the time-shift map due to temperature rise (a local effect, occurring within the vicinity of the heated region) from the component due to translation and deformation (effect observed over a larger region). A rubber phantom experiment was designed where high intensity focused ultrasound was used to generate localized heating while motion was applied to the phantom and/or imaging transducer. Temperature profiles were successfully estimated while the phantom was translated by 30 mm and axially deformed by 13%.

Quantitative analysis and applications of non-invasive temperature estimation using diagnostic ultrasound

A quantitative analysis of a two-dimensional non-invasive real-time temperature-change estimation algorithm based on diagnostic backscattered ultrasound RF-data is presented in this paper. An experimental system consisting of a therapeutic ultrasound unit and an ultrasound imaging unit was used to quantitatively characterize the accuracy, spatial resolution and ripple artifacts of the temperature estimates in a rubber phantom heating experiment. The ripple is shown to be a consequence of the thermo-acoustic lens effect resulting from local changes of the speed of sound in heated regions. Non-invasive temperature estimates were used as inputs to a multipoint ultrasound phased array temperature controller, for a long duration hyperthermia experiment. The applicability of this method to tissue media, as well as its major limitations are discussed.

Combined imaging and therapy with piezocomposite phased arrays

Recently, the authors have developed temperature estimation algorithms based on signal processing of pulse-echo ultrasound radio frequency (RF) data at diagnostic levels. A modified commercially available scanner was used to obtain 2D temperature estimates that were color coded and overlaid on real-time B-scan images to show the location and extent of the therapeutic beam with respect to the target as well as any critical structures in the treatment region. Recent advances in piezocomposite transducer technology have allowed the development of high power phased arrays for high-intensity focused ultrasound (HIFU) generation with excellent cross coupling characteristics. Furthermore, fractional bandwidths of 30-60 % are now possible with such arrays. Therefore, the authors have investigated the feasibility of utilizing a 64-element piezocomposite therapeutic array in an imaging mode. The array is concave on a spherical shell with a radius of curvature of 100 mm with elements arranged in a linear configuration (2 mm/spl times/50 mm). The array operates at a center frequency of 1.25 MHz and has a fractional bandwidth of 37%. Wire target images as well as images from a tissue mimicking cyst phantom were reconstructed using a synthetic aperture technique. Excellent image quality was achieved in a region extending 70 mm axially and 60 mm laterally and centered around the geometric center of the array. Furthermore, the authors have experimentally established that the speckle generated by this array can be used to extract temperature information based on our previously described algorithm. This was demonstrated by using a 4/spl times/64 matrix switch and a high speed digitizer to acquire image frames during a slow heating experiment.

Combined ultrasound image guidance and therapy using a therapeutic phased array

Ultrasonic imaging has been suggested for guidance of high intensity focused ultrasound therapy. This is typically implemented using two different ultrasonic transducer systems. However the need for two transducers may pose practical difficulties such as alignment and different coordinate systems. In this paper we investigate the possibility of using the same physical transducer array for performing both therapy and imaging. A spherically shaped 1D 64-element high intensity focused ultrasound transducer capable of operating in therapeutic and imaging modes was designed and fabricated. In vitro experiments were conducted to show that this transducer is capable of creating well defined lesions 30-50 mm deep into bovine muscle samples. Furthermore, an experimental pulse-echo system was designed to collect full synthetic aperture data using this transducer. Images of multiple-wire and speckle-generating phantoms are shown to illustrate the imaging capability of this transducer. Although the image quality achieved with this array is inferior to that obtained by conventional diagnostic imaging transducers, it is sufficiently high to produce image features suitable for guidance.

Non-invasive spatio-temporal temperature estimation using diagnostic ultrasound

A method for non-invasively estimating tissue temperatures using 2D diagnostic ultrasound imaging arrays is presented in this paper. It is based on a linear relationship between the apparent speckle pattern displacements and temperature, as seen on acquired A-lines when the sample is heated by external heating fields. The proportionality constant between speckle displacement and temperature is determined by the differential change in the speed of sound due to temperature and the linear coefficient of thermal expansion of the material. Accurate estimation of the displacements and proportionality constant translates into accurate, calibrated, high-resolution (2 mm spatial, sub-/spl deg/C) noninvasive 2D spatio-temporal sample temperature estimates. The mathematical background of this method and experimental results are shown.

A novel Fizzy/Cdc20-dependent mechanism suppresses necrosis in neural stem cells

Cancer stem cells likely survive chemotherapy or radiotherapy by acquiring mutations that inactivate the endogenous apoptotic machinery or by cycling slowly. Thus, knowledge about the mechanisms linking the activation of an alternative cell death modality and the cell cycle machinery could have a transformative impact on the development of new cancer therapies, but the mechanisms remain completely unknown. We investigated the regulation of alternative cell death in Drosophila larval brain neural stem cells (neuroblasts) in which apoptosis is normally repressed. From a screen, we identified two novel loss-of-function alleles of the Cdc20/fizzy (fzy) gene that lead to premature brain neuroblast loss without perturbing cell proliferation in other diploid cell types. Fzy is an evolutionarily conserved regulator of anaphase promoting complex/cyclosome (APC/C). Neuroblasts carrying the novel fzy allele or exhibiting reduced APC/C function display hallmarks of necrosis. By contrast, neuroblasts overexpressing the non-degradable form of canonical APC/C substrates required for cell cycle progression undergo mitotic catastrophe. These data strongly suggest that Fzy can elicit a novel pro-survival function of APC/C by suppressing necrosis. Neuroblasts experiencing catastrophic cellular stress, or overexpressing p53, lose Fzy expression and undergo necrosis. Co-expression of fzy suppresses the death of these neuroblasts. Consequently, attenuation of the Fzy-dependent survival mechanism functions downstream of catastrophic cellular stress and p53 to eliminate neuroblasts by necrosis. Strategies that target the Fzy-dependent survival mechanism might lead to the discovery of new treatments or complement the pre-existing therapies to eliminate apoptosis-resistant cancer stem cells by necrosis.