Naomi R. Miller

Fundamental limitations of noninvasive temperature imaging by means of ultrasound echo strain estimation

Ultrasonic estimation of temperature-induced echo strain has been suggested as a means of predicting the location of thermal lesions formed by focused ultrasound (US) surgery before treatment. Preliminary investigations of this technique have produced optimistic results because they were carried out with rubber phantoms and used room temperature, rather than body temperature, as the baseline. The objective of the present study was to determine, through modelling, the likely feasibility of using ultrasonic temperature imaging to detect and localise the focal region of the heating beam for a medium with a realistic temperature-dependence of sound speed subjected to a realistic temperature rise. We determined the minimum ultrasonic signal-to-noise ratio (SNR) required to visualise the heated region for liver of varying fat content. Due to the small (0.5%) change in sound speed at the focus, the threshold SNR for normal liver (low fat content) was found to be at least 20 dB. This implies that temperature imaging in this tissue type will only be feasible if the effects of electronic noise can be minimised and if other sources of noise, such as cardiac-induced motion, do not substantially reduce the visibility of the focal region. For liver of intermediate fat content, the heated region could not be visualised even when the echo data were noise-free. Tissues with a very high fat content are likely to represent the most favourable conditions for ultrasonic temperature imaging.

Feasibility of using ultrasound for real-time tracking during radiotherapy

This study was designed to examine the feasibility of utilizing transabdominal ultrasound for real-time monitoring of target motion during a radiotherapy fraction. A clinical Acuson 128/XP ultrasound scanner was used to image various stationary and moving phantoms while an Elekta SL25 linear accelerator radiotherapy treatment machine was operating. The ultrasound transducer was positioned to image from the outer edge of the treatment field at all times. Images were acquired to videotape and analyzed using in-house motion tracking algorithms to determine the effect of the SL25 on the quality of the displacement measurements. To determine the effect on the dosimetry of the presence of the transducer, dose distributions were examined using thermoluminescent dosimeters loaded into an Alderson Rando phantom and exposed to a 10×10cm2 treatment field with and without the ultrasound transducer mounted 2.5cm outside the field edge. The ultrasound images acquired a periodic noise that was shown to occur at the pulsing frequency of the treatment machine. Images of moving tissue were analyzed and the standard deviation on the displacement estimates within the tissue was identical with the SL25 on and off. This implies that the periodic noise did not significantly degrade the precision of the tracking algorithm (which was better than 0.01mm). The presence of the transducer at the surface of the phantom presented only a 2.6% change to the dose distribution to the volume of the phantom. The feasibility of ultrasonic motion tracking during radiotherapy treatment is demonstrated. This presents the possibility of developing a noninvasive, real-time and low-cost method of tracking target motion during a treatment fraction.

Speckle tracking in a phantom and feature-based tracking in liver in the presence of respiratory motion using 4D ultrasound

We have evaluated a 4D ultrasound-based motion tracking system developed for tracking of abdominal organs during therapy. Tracking accuracy and precision were determined using a tissue-mimicking phantom, by comparing tracked motion with known 3D sinusoidal motion. The feasibility of tracking 3D liver motion in vivo was evaluated by acquiring 4D ultrasound data from four healthy volunteers. For two of these volunteers, data were also acquired whilst simultaneously measuring breath flow using a spirometer. Hepatic blood vessels, tracked off-line using manual tracking, were used as a reference to assess, in vivo, two types of automated tracking algorithm: incremental (from one volume to the next) and non-incremental (from the first volume to each subsequent volume). For phantom-based experiments, accuracy and precision (RMS error and SD) were found to be 0.78 mm and 0.54 mm, respectively. For in vivo measurements, mean absolute distance and standard deviation of the difference between automatically and manually tracked displacements were less than 1.7 mm and 1 mm respectively in all directions (left-right, anterior-posterior and superior-inferior). In vivo non-incremental tracking gave the best agreement. In both phantom and in vivo experiments, tracking performance was poorest for the elevational component of 3D motion. Good agreement between automatically and manually tracked displacements indicates that 4D ultrasound-based motion tracking has potential for image guidance applications in therapy.

The spatio-temporal strain response of oedematous and nonoedematous tissue to sustained compression in vivo.

Poroelastic theory predicts that compression-induced fluid flow through a medium reveals itself via the spatio-temporal behaviour of the strain field. Such strain behaviour has already been observed in simple poroelastic phantoms using generalised elastographic techniques (Berry et al. 2006a, 2006b). The aim of this current study was to investigate the extent to which these techniques could be applied in vivo to image and interpret the compression-induced time-dependent local strain response in soft tissue. Tissue on both arms of six patients presenting with unilateral lymphoedema was subjected to a sustained compression for up to 500 s, and the induced strain was imaged as a function of time. The strain was found to exhibit time-dependent spatially varying behaviour, which we interpret to be consistent with that of a heterogeneous poroelastic material. This occurred in both arms of all patients, although it was more easily seen in the ipsilateral (affected) arm than in the contralateral (apparently unaffected) arm in five out of the six patients. Further work would appear to be worthwhile to determine if poroelasticity imaging could be used in future both to diagnose lymphoedema and to explore the patho-physiology of the condition.

Performance of ultrasound based measurement of 3D displacement using a curvilinear probe for organ motion tracking

Three-dimensional (3D) soft tissue tracking is of interest for monitoring organ motion during therapy. Our goal is to assess the tracking performance of a curvilinear 3D ultrasound probe in terms of the accuracy and precision of measured displacements. The first aim was to examine the depth dependence of the tracking performance. This is of interest because the spatial resolution varies with distance from the elevational focus and because the curvilinear geometry of the transducer causes the spatial sampling frequency to decrease with depth. Our second aim was to assess tracking performance as a function of the spatial sampling setting (low, medium or high sampling). These settings are incorporated onto 3D ultrasound machines to allow the user to control the trade-off between spatial sampling and temporal resolution. Volume images of a speckle-producing phantom were acquired before and after the probe had been moved by a known displacement (1, 2 or 8 mm). This allowed us to assess the optimum performance of the tracking algorithm, in the absence of motion. 3D speckle tracking was performed using 3D cross-correlation and sub-voxel displacements were estimated. The tracking performance was found to be best for axial displacements and poorest for elevational displacements. In general, the performance decreased with depth, although the nature of the depth dependence was complex. Under certain conditions, the tracking performance was sufficient to be useful for monitoring organ motion. For example, at the highest sampling setting, for a 2 mm displacement, good accuracy and precision (an error and standard deviation of <0.4 mm) were observed at all depths and for all directions of displacement. The trade-off between spatial sampling, temporal resolution and size of the field of view (FOV) is discussed.

Characterization of cardiovascular liver motion for the eventual application of elasticity imaging to the liver in vivo

Elastography, which uses ultrasound to image the tissue strain that results from an applied displacement, can display tumours and heat-ablated tissue with high contrast. However, its application to liver in vivo may be problematic due to the presence of respiratory and cardiovascular sources of displacement. The aim of this study was to measure the cardiovascular-induced component of natural liver motion for the purpose of planning future work that will either use the motion to produce elasticity images or will compensate for it when employing an external source of displacement. A total of 36 sequences of 7 s real-time radio frequency (RF) echo images of the liver were acquired from six healthy volunteers during breath-hold using a stationary 3.5 MHz transducer. For each image sequence, the axial and lateral components of displacement were measured for each pair of consecutive RF images using 2D-echo tracking. The spatio-temporal character of these displacements was then analysed using a novel approach, employing proper orthogonal decomposition, whereby the dominant motion patterns are described by eigenvectors with the highest eigenvalues. The motion patterns of different liver segments were complex, but they were also found to be cyclic, highly repeatable and capable of producing measurable displacements in the liver. These observations provide good evidence to suggest that it may be possible to correct for natural liver motion when using an externally applied displacement for elasticity imaging. It was also found that about 65%-70% of all liver motion could be described using the first eigenvector. Use of only this component of the motion will greatly simplify the design of a mechanical system to be used in an objective study of elasticity imaging of phantoms and excised tissues in the presence of simulated cardiovascular-induced liver motion.

Multi-directional in vivo tensile skin stiffness measurement for the design of a reproducible tensile strain elastography protocol.

Elastography is a promising new medical imaging modality, displaying spatial distribution of biomechanical properties such as local tissue strain response to an applied stress. To develop a reproducible test protocol for skin elastography, the effect of various parameters on skin stiffness measurements was investigated.

Thresholds for visual detection of Young's modulus contrast in simulated ultrasound image movies

Elasticity imaging (EI) is being developed to allow the evaluation of the mechanical properties of soft tissue, but these properties are already assessed in routine ultrasound breast examination using a method that involves the subjective interpretation of tissue motion seen in real-time B-mode image movies during palpation. We refer to this method as relative motion assessment (RMA). The purpose of this study was to begin a process of learning about the usefulness and limitations of RMA relative to the emerging method of elasticity imaging. Perception experiments were performed to measure Youngs modulus contrast thresholds for positive contrast lesions under controlled conditions that could subsequently be repeated to evaluate elasticity imaging for the same task. Observer ability to grade relative lesion contrast using RMA was also assessed. Simulated sequences of B-scans of tissue moving in response to an applied force were generated and used in a two-alternative forced-choice (2-AFC) experiment to measure contrast thresholds for the detection of disc-shaped elastic lesions by RMA in the absence of ultrasound echo contrast. Results were obtained for four observers at a lesion area of about 77 speckle cells and for five observers at lesion areas of about 42 and 139 speckle cells. Youngs modulus contrast thresholds were found to decrease with increasing lesion size and were well within the range of contrast values that have been measured for breast tumours in vitro. It was also found that observers were quite skilled at using RMA to grade the relative strain contrast of lesions. The nonlinear relationship between the object contrast (Youngs modulus contrast) and the image contrast (strain contrast) prevented observers from detecting very small lesions with 100% accuracy, no matter how high the object contrast. A preliminary comparison of the results for RMA with published thresholds for elastography indicated that elastography is likely to offer great benefit in reducing modulus contrast thresholds, but further study is required to confirm this.

Ultrasound Elastography of the Skin and Subcutis under Surface Extensive Loading

Measurement of skin elasticity has the potential to aid clinical diagnosis of a range of skin conditions. Our eventual goal is to develop an ultrasonic method for imaging the elasticity of the skin and subcutaneous tissue, and to use this technique to study skin cancer and lymphoedema. The aim of the present study was to investigate the effects of surface extensive loading, of varying direction, on the strain generated within normal skin and the underlying tissue layers. Extensive strains were applied to the surface of normal skin, while measuring the load and acquiring a sequence of ultrasound B-mode images. Correlation-based displacement tracking was used to generate displacement images from the ultrasound images. Least squares strain estimation then formed strain images, known as elastograms, of field size 18 mm (depth) by 28 mm (width). Propagation of strain into the subcutis was observed, suggesting that the technique could be useful in studying lymphoedema. Less strain was generated in underlying muscle. Confirmation of a previously observed anisotropy was obtained, as a modulation factor of about two and a periodicity of 90°, for the variation of stiffness with direction of loading.

The effect of object speed and direction on the performance of 3D speckle tracking using a 3D swept-volume ultrasound probe.

Three-dimensional (3D) soft tissue tracking using 3D ultrasound is of interest for monitoring organ motion during therapy. Previously we demonstrated feature tracking of respiration-induced liver motion in vivo using a 3D swept-volume ultrasound probe. The aim of this study was to investigate how object speed affects the accuracy of tracking ultrasonic speckle in the absence of any structural information, which mimics the situation in homogenous tissue for motion in the azimuthal and elevational directions. For object motion prograde and retrograde to the sweep direction of the transducer, the spatial sampling frequency increases or decreases with object speed, respectively. We examined the effect object motion direction of the transducer on tracking accuracy. We imaged a homogenous ultrasound speckle phantom whilst moving the probe with linear motion at a speed of 0-35 mm s⁻¹. Tracking accuracy and precision were investigated as a function of speed, depth and direction of motion for fixed displacements of 2 and 4 mm. For the azimuthal direction, accuracy was better than 0.1 and 0.15 mm for displacements of 2 and 4 mm, respectively. For a 2 mm displacement in the elevational direction, accuracy was better than 0.5 mm for most speeds. For 4 mm elevational displacement with retrograde motion, accuracy and precision reduced with speed and tracking failure was observed at speeds of greater than 14 mm s⁻¹. Tracking failure was attributed to speckle de-correlation as a result of decreasing spatial sampling frequency with increasing speed of retrograde motion. For prograde motion, tracking failure was not observed. For inter-volume displacements greater than 2 mm, only prograde motion should be tracked which will decrease temporal resolution by a factor of 2. Tracking errors of the order of 0.5 mm for prograde motion in the elevational direction indicates that using the swept probe technology speckle tracking accuracy is currently too poor to track homogenous tissue over a series of volume images as these errors will accumulate. Improvements could be made through increased spatial sampling in the elevational direction.