.

.

.

.

Abstract The routine clinical use of diagnostic ultrasound (US) has spread considerably worldwide in recent decades. This is due in large part to the availability of US probes that enable a wide range of clinical applications as well as provide performance benefits arising from technological improvements. This paper describes the current commercially available US probe types, lists some of their clinical applications and briefly explains the technologies that are responsible for recent enhancements in image quality and ergonomics. Our intention is to summarize information that will allow healthcare professionals to select the appropriate probe for the intended use and the desired performance-price ratio..

.

.

.

.

.

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users..

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users..

.

.

.

.

.

.

.

.

.

.

Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, we used MRE to quantify (kPa) the elasticity modulus Gd and viscosity modulus Gl of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, we found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on Gd and Gl parametric maps. The most circumscribed tumor (U-87 MG glioma) was the stiffest, whereas the most infiltrative tumor (MDA-MB-231 metastatic breast carcinoma) was the softest. Tumor cell density and microvessel density correlated significantly and positively with elasticity and viscosity, whereas there was no association with the extent of collagen deposition or myelin fiber entrapment. In conclusion, although malignant tumors tend to exhibit increased rigidity, intracranial tumors presented as remarkably softer than normal brain parenchyma. Our findings reinforce the case for MRE use in diagnosing and staging brain malignancies, based on the association of different tumor phenotypes with different mechanical properties..

.

.

.

.

.

.

In modern radiotherapy, verification of the treatment to ensure the target receives the prescribed dose and normal tissues are optimally spared has become essential. Several forms of image guidance are available for this purpose. The most commonly used forms of image guidance are based on kilovolt or megavolt x-ray imaging. Image guidance can also be performed with non-harmful ultrasound (US) waves. This increasingly used technique has the potential to offer both anatomical and functional information.This review presents an overview of the historical and current use of two-dimensional and three-dimensional US imaging for treatment verification in radiotherapy. The US technology and the implementation in the radiotherapy workflow are described. The use of US guidance in the treatment planning process is discussed. The role of US technology in inter-fraction motion monitoring and management is explained, and clinical studies of applications in areas such as the pelvis, abdomen and breast are reviewed. A companion review paper (O'Shea et al 2015 Phys. Med. Biol. submitted) will extensively discuss the use of US imaging for intra-fraction motion quantification and novel applications of US technology to RT. .

The objective of this study was to assess the in vivo performance of our 2-D locally regularized strain estimation method with 35 breast lesions, mainly cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as well as the method's adaptability, led to an algorithm that is able to track tissue motion from radiofrequency ultrasound images acquired in clinical conditions. Particular attention was paid to strain estimation reliability, implying analysis of the mean normalized correlation coefficient maps. For all lesions examined, the results indicated that strain image interpretation, as well as its comparison with B-mode data, should take into account the information provided by the mean normalized correlation coefficient map. Different trends were observed in the tissue response to compression. In particular, carcinomas appeared larger in strain images than in B-mode images, resulting in a mean strain/B-mode lesion area ratio of 2.59 ± 1.36. In comparison, the same ratio was assessed as 1.04 ± 0.26 for fibroadenomas. These results are in agreement with those of previous studies, and confirm the interest of a more thorough consideration of size difference as one parameter discriminating between malignant and benign lesions. .

BACKGROUND: Magnetic resonance elastography (MRE) is an emerging imaging technique that affords non-invasive quantitative assessment and visualization of tissue mechanical properties in vivo. METHODS: In this study, MRE was used to quantify (kPa) the absolute value of the complex shear modulus |G*|, elasticity Gd and viscosity Gl of SW620 human colorectal cancer xenografts before and 24 h after treatment with either 200 mg kg(-1) of the vascular disrupting agent ZD6126 (N-acetylcolchinol-O-phosphate) or vehicle control, and the data were compared with changes in water diffusivity measured by diffusion-weighted magnetic resonance imaging. RESULTS: A heterogeneous distribution of |G*|, Gd and Gl was observed pre-treatment with an intertumoral coefficient of variation of 13% for |G*|. There were no significant changes in the vehicle-treated cohort. In contrast, ZD6126 induced a significant decrease in the tumour-averaged |G*| (P<0.01), Gd (P<0.01) and Gl (P<0.05), and this was associated with histologically confirmed central necrosis. This reduction in tumour viscoelasticity occurred at a time when no significant change in tumour apparent diffusion coefficient (ADC) was observed. CONCLUSIONS: These data demonstrate that MRE can provide early imaging biomarkers for treatment-induced tumour necrosis..

Focal symptomatic epilepsy is the most common form of epilepsy that can often be cured with surgery. A small proportion of patients with focal symptomatic epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI). The most common pathology in this group is type II focal cortical dysplasia (FCD), which is a subtype of malformative brain lesion associated with medication-resistant epilepsy. We present a patient with MRI-negative focal symptomatic epilepsy who underwent invasive electrode recordings. At the time of surgery, a novel ultrasound-based technique called ShearWave Elastography (SWE) was performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B-mode ultrasound and 3-T MRI. Electroencephalography (EEG), positron emission tomography (PET), and magnetoencephalography (MEG) scans demonstrated an abnormality in the right frontal region. On the basis of this finding, a depth electrode was implanted into the lesion. Surgical resection and histology confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. .

.

.

This study investigates the use of a mechanically-swept 3D ultrasound (3D-US) probe for soft-tissue displacement monitoring during prostate irradiation, with emphasis on quantifying the accuracy relative to CyberKnife® x-ray fiducial tracking. An US phantom, implanted with x-ray fiducial markers was placed on a motion platform and translated in 3D using five real prostate motion traces acquired using the Calypso system. Motion traces were representative of all types of motion as classified by studying Calypso data for 22 patients. The phantom was imaged using a 3D swept linear-array probe (to mimic trans-perineal imaging) and, subsequently, the kV x-ray imaging system on CyberKnife. A 3D cross-correlation block-matching algorithm was used to track speckle in the ultrasound data. Fiducial and US data were each compared with known phantom displacement. Trans-perineal 3D-US imaging could track superior-inferior (SI) and anterior-posterior (AP) motion to ≤0.81 mm root-mean-square error (RMSE) at a 1.7 Hz volume rate. The maximum kV x-ray tracking RMSE was 0.74 mm, however the prostate motion was sampled at a significantly lower imaging rate (mean: 0.04 Hz). Initial elevational (right-left; RL) US displacement estimates showed reduced accuracy but could be improved (RMSE <2.0 mm) using a correlation threshold in the ultrasound tracking code to remove erroneous inter-volume displacement estimates. Mechanically-swept 3D-US can track the major components of intra-fraction prostate motion accurately but exhibits some limitations. The largest US RMSE was for elevational (RL) motion. For the AP and SI axes, accuracy was sub-millimetre. It may be feasible to track prostate motion in 2D only. 3D-US also has the potential to improve high tracking accuracy for all motion types. It would be advisable to use US in conjunction with a small (∼2.0 mm) centre-of-mass displacement threshold in which case it would be possible to take full advantage of the accuracy and high imaging rate capability. .

BACKGROUND/AIMS: 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. METHODS: The parameters investigated were: history of skin loading before test loading (preconditioning), direction of test loading (anisotropy) and posture (pre-stress). If a sample of skin is loaded, its stiffness will temporarily change. Finally, the reproducibility of skin stiffness and anisotropy measurements, using the developed techniques, was investigated. RESULTS: By measuring how the stiffness changed with different time delays between loading cycles, the time required for healthy skin to return to its original pre-loaded state was in the region of 125 s. A second finding, which supports and extends previous work, was that skin stiffness varied with direction, by an approximate factor of 2, and that anisotropy was less apparent with preconditioned skin than non-preconditioned skin. Study of the effect of posture showed that care needs to be taken over which stiffness measure is used. For example, measurement of the load at a given displacement was found to be highly dependent on posture, whereas measurement of the phase III stiffness was independent of posture. CONCLUSION: It was shown that when the measurement variables and methods of analysis were standardised, skin stiffness could be measured reproducibly enough to distinguish between the stiffest and softest directions, and that these methods allowed formation of skin elastograms free from confounding influences..

For clinical optoacoustic imaging, linear probes are preferably used because they allow versatile imaging of the human body with real-time display and free-hand probe guidance. The two-dimensional (2-D) optoacoustic image obtained with this type of probe is generally interpreted as a 2-D cross-section of the tissue just as is common in echo ultrasound. We demonstrate in three-dimensional simulations, phantom experiments, and in vivo mouse experiments that for vascular imaging this interpretation is often inaccurate. The cylindrical blood vessels emit anisotropic acoustic transients, which can be sensitively detected only if the direction of acoustic radiation coincides with the probe aperture. Our results reveal for this reason that the signal amplitude of different blood vessels may differ even if the vessels have the same diameter and initial pressure distribution but different orientation relative to the imaging plane. This has important implications for the image interpretation, for the probe guidance technique, and especially in cases when a quantitative reconstruction of the optical tissue properties is required..

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts..

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography..

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way..

High-intensity focused ultrasound (HIFU) is rapidly gaining acceptance as a non-invasive method for soft tissue tumor ablation, but improvements in the methods of treatment delivery, planning and monitoring are still required. Backscatter temperature imaging (BTI) uses ultrasound to visualize heating-induced echo strain and may be used to indicate the position of the HIFU focal region using low-power "sub-lesioning" exposure. The technique may also provide a quantitative tool for assessing the efficacy of treatment delivery if apparent strain measurements can be related to the underlying temperature rise. To obtain temperature estimates from strain measurements, the relationship between these variables has to be either measured or otherwise assumed from previous calibrations in similar tissues. This article describes experimental measurements aimed at deriving the relationship between temperature rise and apparent strain in the laboratory environment using both ex vivo bovine liver tissue samples and normothermically perfused porcine livers. A BTI algorithm was applied to radiofrequency ultrasound echo data acquired from a clinical ultrasound scanner (Z.One, Zonare Medical Systems, Mountain View, CA, USA) where the imaging probe was aligned with the focal region of a HIFU transducer. Temperature measurements were obtained using needle thermocouples implanted in the liver tissue. A series of "non-ablative" HIFU exposures giving peak temperatures below 10°C were made in three separate ex vivo bovine livers, yielding an average strain/temperature coefficient of 0.126 ± 0.088 percentage strain per degree Celsius. In the perfused porcine livers at a starting temperature of 38°C (normal body temperature) the strain/temperature coefficients were found to be 0.040 ± 0.029 percentage strain per degree Celsius. The uncertainty in these results is directly linked to the precision of the strain measurement, as well as the naturally occurring variance between different tissue samples, indicating that BTI may lack the accuracy required to be implemented successfully in practice as a quantitative treatment planning technique at a sub-lesioning exposure level. This is because, to be of use in treatment planning, temperature-rise estimates may require an accuracy greater (<10%) than that offered by BTI measurement. BTI may, however, still play a role in ensuring the correct positioning of the focal region and as a treatment monitoring modality capable of detecting an increased rate of heating in tissue after HIFU ablation..

Recent advances have led to a multitude of image modalities being used for visualization of tissue stiffness. High-resolution images of tissue stiffness are desirable, as they have the potential to provide useful diagnostic information. A noncontact optical imaging method has the attractions of low cost, simplicity, and utility when skin contact is undesirable. However, previous optical techniques have required the application of paint or ink to the surface of the skin and so have required contact. Therefore, the present study assessed the feasibility of tracking skin surface topography to produce elastograms. The study showed, by analyzing a variety of silicone skin surface replicas from various body sites of subjects of different ages, that skin surface elastography by tracking surface topography would be feasible. The study further showed that the quality of the strain images can be optimized by measuring skin line pattern frequency. Skin samples with high skin line frequency will achieve best spatial resolution, in the order of 1 mm, comparable to contact techniques reported previously. A mechanically inhomogeneous silicone replica was then imaged, illustrating the technique's ability to detect strain contrast. Finally, the feasibility of implementing the technique in vivo was illustrated using a single pigmented skin lesion..

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR–VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR–VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR–VMAT trajectory, was determined using Dijkstra's algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts..

Identification of the anatomical location and mechanical properties such as adherence at the tissue tumour interface may be of clinical benefit in determination of tumour resectability and prognosis. There are currently no imaging modalities in routine clinical practice that can provide this information. This paper presents the development of a new imaging technique based on ultrasound elastography, called slip elastography, for determination of the anatomical location and measurement of the adherence between two surfaces. The theoretical basis of slip and its definition in relation to shear are described. In vitro testing with gelatine phantoms to determine the optimal parameters for shear strain estimation and slip boundary measurement and to test reliability are also described. The results suggest that slip elastography can reliably identify the anatomical location of a slip boundary and can measure the externally applied axial force required to initiate slip at that boundary in vitro. The vector based shear strain estimator was the most robust and worked with minimal angular dependence with minimal non-slip shearing artefact..

A photoacoustic (PA) spectroscopy system has been built to study small samples, particularly the differences between the PA spectra of oxygenated and deoxygenated blood, and various PA contrast agents, with view to optimising the indentifying these media, in clinical PA images. Short (ns) pulses of light from one of two OPO lasers are delivered into a 1mm diameter cylindrical sample holder. The wavelength is scanned over the range 400-700 nm or 690-950nm (depending on laser used) using a different pulse for each wavelength. Sensitive measurement of the thermoacoustic pressure wave energy emitted from the end of the sample, which acts like a disc-shaped piston source, is facilitated by placing it at the focus of a strongly focused ultrasound transducer. The resulting optical spectra are corrected for some system variables, such as the wavelength-dependent laser energy. Further corrections are planned, so that the measurement is truly of optical absorption coefficient at each wavelength. Even without these additional corrections however, the measured PA spectra of oxygenated blood and gold nano-rods strongly resemble their published optical absorption spectra. In addition to its intended use this system may have applications as a laboratory spectrophotometer, suitable for use with optically dark and turbid media..

Photoacoustic imaging, based on ultrasound detected after laser irradiation, is an extension to diagnostic ultrasound for imaging the vasculature, blood oxygenation and the uptake of optical contrast media with promise for cancer diagnosis. For versatile scanning, the irradiation optics is preferably combined with the acoustic probe in an epi-style arrangement avoiding acoustically dense tissue in the acoustic propagation path from tissue irradiation to acoustic detection. Unfortunately epiphotoacoustic imaging suffers from strong clutter, arising from optical absorption in tissue outside the image plane, and from acoustic backscattering. This limits the imaging depth for useful photoacoustic image contrast to typically less than one centimeter. Deformation-compensated averaging (DCA), which takes advantage of clutter decorrelation induced by palpating the tissue with the imaging probe, has previously been proposed for clutter reduction. We demonstrate for the first time that DCA results in reduced clutter in real-time freehand clinical epiphotoacoustic imaging. For this purpose, combined photoacoustic and pulse-echo imaging at 10-Hz frame rate was implemented on a commercial scanner, allowing for ultrasound-based motion tracking inherently coregistered with photoacoustic frames. Results from the forearm and the neck confirm that contrast is improved and imaging depth increased by DCA..

The effectiveness of intensity-modulated radiation therapy (IMRT) is compromised by involuntary motion (e.g. respiration, cardiac activity). The feasibility of processing ultrasound echo data to automatically estimate 3D liver motion for real-time IMRT guidance was previously demonstrated, but performance was limited by an acquisition speed of 2 volumes per second due to hardware restrictions of a mechanical linear array probe. Utilizing a 2D matrix array probe with parallel receive beamforming offered increased acquisition speeds and an opportunity to investigate the benefits of higher volume rates. In vivo livers of three volunteers were scanned with and without respiratory motion at volume rates of 24 and 48 Hz, respectively. Respiration was suspended via voluntary breath hold. Correlation-based, phase-sensitive 3D speckle tracking was applied to consecutively acquired volumes of echo data. Volumes were omitted at fixed intervals and 3D speckle tracking was re-applied to study the effect of lower scan rates. Results revealed periodic motion that corresponded with the heart rate or breathing cycle in the absence or presence of respiration, respectively. For cardiac-induced motion, volume rates for adequate tracking ranged from 8 to 12 Hz and was limited by frequency discrepancies between tracking estimates from higher and lower frequency scan rates. Thus, the scan rate of volume data acquired without respiration was limited by the need to sample the frequency induced by the beating heart. In respiratory-dominated motion, volume rate limits ranged from 4 to 12 Hz, interpretable from the root-mean-squared deviation (RMSD) from tracking estimates at 24 Hz. While higher volume rates yielded RMSD values less than 1 mm in most cases, lower volume rates yielded RMSD values of 2-6 mm..

This article presents a new method for acquiring three-dimensional (3-D) volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. Acquisition of a volume takes 15-20 s. A strain volume is then calculated by comparing frame pairs throughout the sequence. The method uses strain quality estimates to automatically pick out high quality frame pairs, and so does not require careful control of the axial compression. In a series of in vitro and in vivo experiments, we quantify the image quality of the new method and also assess its ease of use. Results are compared with those for the current best alternative, which calculates strain between two complete volumes. The volume pair approach can produce high quality data, but skillful scanning is required to acquire two volumes with appropriate relative strain. In the new method, the automatic quality-weighted selection of image pairs overcomes this difficulty and the method produces superior quality images with a relatively relaxed scanning technique..

Melanoma cells can switch between an elongated mesenchymal-type and a rounded amoeboid-type migration mode. The rounded 'amoeboid' form of cell movement is driven by actomyosin contractility resulting in membrane blebbing. Unlike elongated A375 melanoma cells, rounded A375 cells do not display any obvious morphological front-back polarisation, although polarisation is thought to be a prerequisite for cell movement. We show that blebbing A375 cells are polarised, with ezrin (a linker between the plasma membrane and actin cytoskeleton), F-actin, myosin light chain, plasma membrane, phosphatidylinositol (4,5)-bisphosphate and β1-integrin accumulating at the cell rear in a uropod-like structure. This structure does not have the typical protruding shape of classical leukocyte uropods, but, as for those structures, it is regulated by protein kinase C. We show that the ezrin-rich uropod-like structure (ERULS) is an inherent feature of polarised A375 cells and not a consequence of cell migration, and is necessary for cell invasion. Furthermore, we demonstrate that membrane blebbing is reduced at this site, leading to a model in which the rigid ezrin-containing structure determines the direction of a moving cell through localised inhibition of membrane blebbing..

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..

Advanced radiation techniques such as intensity-modulated radiotherapy (IMRT) for complex geometries in which targets are close to organs at risk have been introduced in radiation therapy, creating a need for procedures that allow easy three-dimensional (3-D) measurement of dose for verification purposes. Polymer gels that change their material properties when irradiated have been suggested for such use. For example, the change in their magnetic properties has been thoroughly investigated with magnetic resonance imaging (MRI). Also, we have previously shown that the mechanical stiffness, i.e., Young's modulus, of these gels changes with dose. This finding prompted us to assess whether we can image a radiation-induced stiffness distribution with quantitative ultrasound elastography and whether the stiffness distribution is correlated with the dose distribution. A methacrylic-acid-based gel was loaded with scatterers to create an ultrasound echoic signal. It was irradiated to create a rod-like region of increased stiffness with a 10 x 10 mm(2) cross-section. The gel block was compressed in a frame that restricted the movement of the gel to planes orthogonal to the long axis of the irradiated region and ultrasonic echo data were acquired in the central plane during compression. This simplified irradiation pattern and experimental set-up were designed to approximate plane-strain conditions and was chosen for proof of concept. The movement of the gel was tracked from ultrasound images of a different compressional state using cross-correlation, enabling a displacement map to be created. The shear modulus was reconstructed using an inverse algorithm. The role of the magnitude of the regularization parameter in the inverse problem and the boundary conditions in influencing the spatial distribution of stiffness and, thus, final dose contrast was investigated through parametric studies. These parameters were adjusted using prior knowledge about the stiffness in parts of the material, e.g., the background was not irradiated and therefore its stiffness was homogeneous. It was observed that a suitable choice for these reconstruction parameters was essential for a quantitative application of stiffness measurement such as dosimetry. The dose contrast and distribution found with the optimal parameters were close to those obtained with MRI. Initial results reported in this article are encouraging and indicate that with ongoing refinement of ultrasound elastography techniques and accompanying inverse algorithms, this approach could play an important role in gel dosimetry..

.

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..

A technique for generating contrast in two-dimensional shear strain elastograms from a localized stress is presented. The technique involves generating a non-uniform, localized stress via a magnetically actuated implant. Its effectiveness is demonstrated using finite-element simulations and a phantom study provides experimental verification of this. The method is applied to a superficial cancerous lesion model represented as a stiff inclusion in normal tissue. The lesion was best distinguished from its surroundings using total shear strain elastograms, rather than individual strain components. In experimental phantom studies, the lesion was imaged using optical coherence tomography (OCT) and could still be distinguished in elastograms when not readily identifiable in standard OCT images..

Standard test tools have been evaluated for the assessment of safety associated with a prototype transducer intended for a novel radiation force elastographic imaging system. In particular, safety has been evaluated by direct measurement of temperature rise, using a standard thermal test object, and detection of inertial cavitation from acoustic emission. These direct measurements have been compared with values of the thermal index and mechanical index, calculated from acoustic measurements in water using standard formulae. It is concluded that measurements using a thermal test object can be an effective alternative to the calculation of thermal index for evaluating thermal hazard. Measurement of the threshold for cavitation was subject to considerable variability, and it is concluded that the mechanical index still remains the preferred standard means for assessing cavitation hazard..

Radiation-sensitive polymer gels for clinical dosimetry have been intensively investigated with magnetic resonance imaging (MRI) because the transversal magnetic relaxation time is dependent on irradiation dose. MRI is expensive and not easily available in most clinics. For this reason, low-cost, quick and easy-to-use potential alternatives such as optical computed tomography (CT), x-ray CT or ultrasound attenuation CT have also been studied by others. Here, we instead evaluate the dose dependence of the elastic material property, Young's modulus and the dose response of the viscous relaxation of radiation-sensitive gels to discuss their potential for dose imaging. Three batches of a radiation-sensitive polymer gel (MAGIC gel) samples were homogeneously irradiated to doses from 0 Gy to 45.5 Gy. Young's modulus was computed from the measured stress on the sample surface and the strain applied to the sample when compressing it axially, and the viscous relaxation was determined from the stress decay under sustained compression. The viscous relaxation was found not to change significantly with dose. However, Young's modulus was dose dependent; it approximately doubled in the gels between 0 Gy and 20 Gy. By fitting a second-order polynomial to the Young's modulus-versus-dose data, 99.4% of the variance in Young's modulus was shown to be associated with the change in dose. The precision of the gel production, irradiation and Young's modulus measurement combined was found to be 4% at 2 Gy and 3% at 20 Gy. Potential sources of measurement error, such as those associated with the boundary conditions in the compression measurement, inhomogeneous polymerization, temperature (up to 1% error) and the evaporation of water from the sample (up to 1% error), were estimated and discussed. It was concluded that Young's modulus could be used for dose determination. Imaging techniques such as elastography may help to achieve this if they can provide a local measurement of Young's modulus, which may eliminate problems associated with the boundaries (e.g. variation in coefficient of friction) and inhomogeneous polymerization. Elastography combined with a calibration should also be capable of mapping dose in three dimensions..

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..

The optical appearance of human skin is highly dependent on the interaction between the illumination (type and position), observer position and the skin surface structure. Different currently available photographic techniques record different aspects of this appearance, each providing its own incomplete description. This limits their usefulness, especially for pigmented skin lesion diagnosis. In this paper a new, easy to use, low-cost photographic method is described,which aims to generate an efficiently encoded yet reasonably complete representation of skin appearance..

.

.

High-resolution ultrasound-reflex transmission imaging is a non-invasive method that can be performed in vivo. We have adapted and refined this technique for skin imaging. Scans can be analyzed to produce objective parameters. Previous work has highlighted sonographic differences between benign and malignant lesions. The aim of this study was to produce and test numerical parameters from ultrasound skin images that would quantify the acoustic differences between common pigmented lesions, which may aid their discrimination from melanoma. We report our findings for randomly selected patients referred from primary care with suspected melanoma. Those subsequently classified as malignant melanoma (MM), seborrheic keratosis (SK), and benign nevi by a consultant dermatologist (n=87) were imaged by high-resolution ultrasound-reflex transmission imaging. Using surrounding normal skin as a control, numerical sonographic parameters were derived for each lesion giving a relative measure of surface sound reflectance, intra-lesional sound reflection, total sound attenuation, and the relative uniformity of each parameter across the tumor. Significant quantitative differences existed between benign and malignant pigmented lesions studied. Sufficient discrimination was produced between MM (n=25), SKs (n=24) and other benign-pigmented lesions (n=38) to potentially reduce the referral of benign tumors by 65% without missing melanoma..

This paper presents a new multi-light source photometric stereo system for reconstructing images of various characteristics of non-Lambertian rough surfaces with widely varying texture and specularity. Compared to the traditional three-light photometric stereo method, extra lights are employed using a hierarchical selection strategy to eliminate the effects of shadows and specularities, and to make the system more robust. We also show that six lights is the minimum needed in order to apply photometric stereo to the entire visible surface of any convex object. Experiments on synthetic and real scenes demonstrate that the proposed method can extract surface reflectance and orientation effectively, even in the presence of strong shadows and highlights. Hence, the method offers advantages in the recovery of dichromatic surfaces possessing rough texture or deeply relieved topographic features, with applications in reverse engineering and industrial surface inspection. Experimental results are presented in the paper..

Achieving specificity of delivery represents a major problem limiting the clinical application of retroviral vectors for gene therapy, whilst lack of efficiency and longevity of gene expression limit non-viral techniques. Ultrasound and microbubble contrast agents can be used to effect plasmid DNA delivery. We therefore sought to evaluate the potential for ultrasound/microbubble-mediated retroviral gene delivery..

The use of impulsive acoustic radiation force for transient strain imaging was investigated and compared with conventional elastography. A series of experiments were performed to evaluate the performances of the technique on gelatine phantoms containing inclusions and to determine a range of applications where radiation force elastography may be useful compared with static elastography. Slip boundaries and cylindrical inclusions of varying elastic modulus were placed in background materials. A focused ultrasound transducer was used to apply localised radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain radio- frequency echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions. The highly localised and transient strain that is produced at depth permits the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography, due to greater independence from boundary conditions. In particular, radiation force elastograms were more homogeneous in the background and within the inclusions and displayed a superior contrast-transfer-efficiency, particularly for regions that had negative modulus contrast or that were disconnected from the background or the anterior medium by a low friction boundary..

.

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..

Research on polymer-gel dosimetry has been driven by the need for three-dimensional dosimetry, and because alternative dosimeters are unsatisfactory or too slow for that task. Magnetic resonance tomography is currently the most well-developed technique for determining radiation-induced changes in polymer structure, but quick low-cost alternatives remain of significant interest. In previous work, ultrasound attenuation and speed of sound were found to change as a function of absorbed radiation dose in polymer-gel dosimeters, although the investigations were restricted to one ultrasound frequency. Here, the ultrasound attenuation coefficient mu in one polymer gel (MAGIC) was investigated as a function of radiation dose D and as a function of ultrasonic frequency f in a frequency range relevant for imaging dose distributions. The nonlinearity of the frequency dependence was characterized, fitting a power-law model mu = af(b); the fitting parameters were examined for potential use as additional dose readout parameters. In the observed relationship between the attenuation coefficient and dose, the slopes in a quasi-linear dose range from 0 to 30 Gy were found to vary with the gel batch but lie between 0.0222 and 0.0348 dB cm(-1) Gy(-1) at 2.3 MHz, between 0.0447 and 0.0608 dB cm(-1) Gy(-1) at 4.1 MHz and between 0.0663 and 0.0880 dB cm(-1) Gy(-1) at 6.0 MHz. The mean standard deviation of the slope for all samples and frequencies was 15.8%. The slope was greater at higher frequencies, but so were the intra-batch fluctuations and intra-sample standard deviations. Further investigations are required to overcome the observed variability, which was largely associated with the sample preparation technique, before it can be determined whether any frequency is superior to others in terms of accuracy and precision in dose determination. Nevertheless, lower frequencies will allow measurements through larger samples. The fit parameter a of the frequency dependence, describing the attenuation coefficient at 1 MHz, was found to be dose dependent, which is consistent with our expectations, as polymerization is known to be associated with increased absorption of ultrasound. No significant dose dependence was found for the fit parameter b, which describes the nonlinearity with frequency. This is consistent with the increased absorption being due to the introduction of new relaxation processes with characteristic frequencies similar to those of existing processes. The data presented here will help with optimizing the design of future 3D dose-imaging systems using ultrasound methods..

.

High-resolution ultrasound (HRU) is a relatively cheap imaging method that shows small quantitative differences between benign naevi and melanoma. Previous studies using B-mode display suggest that these arise from their differing attenuating properties. Attenuation characteristics, however, are better evaluated using reflex transmission imaging (RTI). White light clinical (WLC) photography is an even cheaper imaging method that is routinely used for monitoring but less frequently in everyday diagnosis. As features from each method may have an independent origin, two such modalities may be of greater diagnostic value than either method alone. However, although quantitative analysis of digital photographs is being developed to aid tumour diagnosis, in vivo RTI for the evaluation of pigmented skin lesions has not previously been described. This paper presents the feasibility of performing RTI in vivo and evaluates the reliability of the objective features used. The potential of the combination of quantitative RTI and white light (WL) digital photography data for the classification of pigmented lesions was assessed..

The use of impulsive acoustic radiation force for strain imaging was investigated. A focused ultrasound transducer was used to apply localized radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions, and was seen to vary approximately linearly with Young's modulus of the material. The highly localized and transient strain that is produced may permit the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography because of greater independence from boundary conditions. For example, the characteristic, bi-directional, high strain artefacts attributable to stress concentration, often seen with static elastography at tissue-inclusion interfaces, do not appear using the transient radiation force strain imaging technique..

The ultrasonic measurement and imaging of tissue elasticity is currently under wide investigation and development as a clinical tool for the assessment of a broad range of diseases, but little account in this field has yet been taken of the fact that soft tissue is porous and contains mobile fluid. The ability to squeeze fluid out of tissue may have implications for conventional elasticity imaging, and may present opportunities for new investigative tools. When a homogeneous, isotropic, fluid-saturated poroelastic material with a linearly elastic solid phase and incompressible solid and fluid constituents is subjected to stress, the behaviour of the induced internal strain field is influenced by three material constants: the Young's modulus (E(s)) and Poisson's ratio (nu(s)) of the solid matrix and the permeability (k) of the solid matrix to the pore fluid. New analytical expressions were derived and used to model the time-dependent behaviour of the strain field inside simulated homogeneous cylindrical samples of such a poroelastic material undergoing sustained unconfined compression. A model-based reconstruction technique was developed to produce images of parameters related to the poroelastic material constants (E(s), nu(s), k) from a comparison of the measured and predicted time-dependent spatially varying radial strain. Tests of the method using simulated noisy strain data showed that it is capable of producing three unique parametric images: an image of the Poisson's ratio of the solid matrix, an image of the axial strain (which was not time-dependent subsequent to the application of the compression) and an image representing the product of the aggregate modulus E(s)(1-nu(s))/(1+nu(s))(1-2nu(s)) of the solid matrix and the permeability of the solid matrix to the pore fluid. The analytical expressions were further used to numerically validate a finite element model and to clarify previous work on poroelastography..

.

Ultrasound (US)/microbubble-mediated gene delivery is a technology with many potential advantages suited to clinical application. Previous studies have demonstrated transfection but many are unsatisfactory in respect to the exposure apparatus, lack of definition of the US field or the limitations on parameters that can be explored using clinical diagnostic US machines. We investigated individual exposure parameters using a system minimising experimental artefacts and allowing control of many parameters of the US field. Using a 1-MHz transducer we systematically varied US parameters, the duration of exposure and the microbubble and DNA concentrations to optimise gene delivery. Delivery was achieved, using lipid microbubbles (SonoVue) and clinically acceptable US exposures, to adherent cells at efficiencies of approximately 4%. The acoustic pressure amplitude (0.25 MPa peak-negative), pulse repetition frequency (1-kHz) and duration of exposure (10 s) were important in optimising gene delivery with minimal impact on cell viability. These findings support the hypothesis that varying the physical parameters of US-mediated gene delivery has an affect on both efficiency and cell viability. These data are the first in terms of their thorough exploration of the US parameter space and will be the basis for more-informed approaches to developing clinical applications of this technology..

Ultrasound/microbubble-mediated gene delivery has the potential to be targeted to tissue deep in the body by directing the ultrasound beam following vector administration. Application of this technology would be minimally invasive and benefit from the widespread clinical experience of using ultrasound and microbubble contrast agents. In this study we evaluate the targeting ability and spatial distribution of gene delivery using focused ultrasound..

Soft biological tissue contains mobile fluid. The volume fraction of this fluid and the ease with which it may be displaced through the tissue could be of diagnostic significance and may also have consequences for the validity with which strain images can be interpreted according to the traditional idealizations of elastography. In a previous paper, under the assumption of frictionless boundary conditions, the spatio-temporal behavior of the strain field inside a compressed cylindrical poroelastic sample was predicted (Berry et al. 2006). In this current paper, experimental evidence is provided to confirm these predictions. Finite element modeling was first used to extend the previous predictions to allow for the existence of contact friction between the sample and the compressor plates. Elastographic techniques were then applied to image the time-evolution of the strain inside cylindrical samples of tofu (a suitable poroelastic material) during sustained unconfined compression. The observed experimental strain behavior was found to be consistent with the theoretical predictions. In particular, every sample studied confirmed that reduced values of radial strain advance with time from the curved cylindrical surface inwards towards the axis of symmetry. Furthermore, by fitting the predictions of an analytical model to a time sequence of strain images, parametric images of two quantities, each related to one or more of three poroelastic material constants were produced. The two parametric images depicted the Poisson's ratio (nu(s)) of the solid matrix and the product of the aggregate modulus (H(A)) of the solid matrix with the permeability (k) of the solid matrix to the pore fluid. The means of the pixel values in these images, nu(s) = 0.088 (standard deviation 0.023) and H(A)k = 1.449 (standard deviation 0.269) x 10(-7) m(2) s(-1), were in agreement with values derived from previously published data for tofu (Righetti et al. 2005). The results provide the first experimental detection of the fluid-flow-induced characteristic diffusion-like behavior of the strain in a compressed poroelastic material and allow parameters related to the above material constants to be determined. We conclude that it may eventually be possible to use strain data to detect and measure characteristics of diffusely distributed mobile fluid in tissue spaces that are too small to be imaged directly..

We study the effects of interstitial fluid flow and interstitial fluid drainage on the spatio-temporal response of soft tissue strain. The motivation stems from the ability to measure in vivo strain distributions in soft tissue via elastography, and the desire to explore the possibility of using such techniques to investigate soft tissue fluid flow. Our study is based upon a mathematical model for soft tissue mechanics from the literature. It is a simple generalization of biphasic theory that includes coupling between the fluid and solid phases of the soft tissue, and crucially, fluid exchange between the interstitium and the local microvasculature. We solve the mathematical equations in two dimensions by the finite element method (FEM). The finite element implementation is validated against an exact analytical solution that is derived in the appendix. Realistic input tissue properties from the literature are used in conjunction with FEM modelling to conduct several computational experiments. The results of these lead to the following conclusions: (i) different hypothetical flow mechanisms lead to different patterns of strain relaxation with time; (ii) representative tissue properties show fluid drainage into the local microvasculature to be the dominant flow-related stress/strain relaxation mechanism; (iii) the relaxation time of strain in solid tumours due to drainage into the microvasculature is on the order of 5-10 s; (iv) under realistic applied pressure magnitudes, the magnitude of the strain relaxation can be as high as approximately 0.4% strain (4000 microstrains), which is well within the range of strains measurable by elastography..

.

.

Ultrasonic temperature imaging is a promising technique for guiding focused ultrasound surgery (FUS). The FUS system is run at an initial, nonablative intensity and a diagnostic transducer images the heat-induced echo strain, which is proportional to the temperature rise. The echo strain image portrays an elliptical "hot spot" corresponding to the focal region of the therapy transducer. It is anticipated that such images will be used to predict the location of the thermal lesion that would be produced at an ablative intensity. We demonstrated in vitro that heat-induced echo strain images can visualize a spatial peak temperature rise of <2 degrees C (starting at room temperature). However, the imaging beam was perpendicular to the treatment beam in these experiments, whereas the most convenient approach in vivo would be to mount the imaging probe within the housing of the therapy transducer such that the two beams are coaxial. A previous simulation experiment predicted that echo strain images would be noisier for the coaxial configuration because sharp lateral gradients in axial displacement cause increased RF signal decorrelation within the beam width. The aim of the current study was to verify this prediction in vitro. We found, that for a temperature rise of approximately 4 degrees C, the mean contrast-to-noise ratio for coaxial and perpendicular echo strain images was 0.37 (+/-0.24) and 2.00 (+/-0.72) respectively. Furthermore, the decorrelation noise seen in the coaxial images obscured the posterior axial border of the hot spot. We conclude that the coaxial configuration will be useful for localizing the hot spot in the lateral direction. However, it may not be able to depict the axial extent of the hot spot or to portray a parameter that is directly related to temperature rise..

.

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 x 10 cm2 treatment field with and without the ultrasound transducer mounted 2.5 cm 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 0.01 mm). 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..

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..

Ultrasonic estimation of heat-induced echo strain has been suggested as a noninvasive technique for guiding focused ultrasound (US) surgery (FUS), that is, for predicting the location of the thermal lesion before it is formed. The proposed strategy is to run the FUS system at a nonablative intensity and to use a diagnostic transducer to image the heat-induced echo strain, which, over a sufficiently small temperature range, is proportional to the temperature rise. The principal aim of this in vitro study was to determine if temperature-induced strain imaging is likely to be able to visualise the small (< 0.5%) strains that one would be restricted to in vivo. Temperature rises ranging from approximately 2 degrees C to 15 degrees C (starting at approximately 25 degrees C) were induced in bovine liver samples using an FUS system. The pre- and post-heated US images were processed to produce images of the apparent axial strain. These images were found to possess excellent spatial and contrast resolution, so that the hot spot remained clearly visible even when the spatial peak strain value was approximately 0.2% (corresponding to temperature rises on the order of 2 to 5 degrees C). Good repeatability in the strain images was observed within and between tissue samples. Artefacts due to thermoacoustic refraction were seen distal to the heated region, but they did not reduce hot spot visibility. The length of the hot spot exceeded that of the subsequent ablation (by approximately 200%), which was to be expected given that temperature imaging depicts the entire area over which the temperature has increased relative to the baseline. We conclude that temperature-induced strain imaging for the guidance of FUS in the liver is likely to be feasible, provided that it will be possible either to neglect or to correct for the additional sources of error (such as cardiac-induced motion) that will arise in vivo..

Ultrasonic estimation of heat-induced echo strain has been suggested as a noninvasive technique for guiding focused ultrasound (US) surgery (FUS), that is, for predicting the location of the thermal lesion before it is formed. The proposed strategy is to run the FUS system at a nonablative intensity and to use a diagnostic transducer to image the heat-induced echo strain, which, over a sufficiently small temperature range, is proportional to the temperature rise. The principal aim of this in vitro study was to determine if temperature-induced strain imaging is likely to be able to visualise the small (< 0.5%) strains that one would be restricted to in vivo. Temperature rises ranging from approximately 2degreesC to 15degreesC (starting at similar to25degreesC) were induced in bovine liver samples using an FUS system. The pre- and post-heated US images were processed to produce images of the apparent axial strain. These images were found to possess excellent spatial and contrast resolution, so that the hot spot remained clearly visible even when the spatial peak strain value was similar to0.2% (corresponding to temperature rises on the order of 2 to 5degreesC). Good repeatability in the strain images was observed within and between tissue samples. Artefacts due to thermoacoustic refraction were seen distal to the heated region, but they did not reduce hot spot visibility. The length of the hot spot exceeded that of the subsequent ablation (by similar to200%), which was to be expected given that temperature imaging depicts the entire area over which the temperature has increased relative to the baseline. We conclude that temperature-induced strain imaging for the guidance of FUS in the liver is likely to be feasible, provided that it will be possible either to neglect or to correct for the additional sources of error (such as cardiac-induced motion) that will arise in vivo. (C) 2004 World Federation for Ultrasound in Medicine Biology..

Recently a new adjoint equation based iterative method was proposed for evaluating the spatial distribution of the elastic modulus of tissue based on the knowledge of its displacement field under a deformation. In this method the original problem was reformulated as a minimization problem, and a gradient-based optimization algorithm was used to solve it. Significant computational savings were realized by utilizing the solution of the adjoint elasticity equations in calculating the gradient. In this paper, we examine the performance of this method with regard to measures which we believe will impact its eventual clinical use. In particular, we evaluate its abilities to (1) resolve geometrically the complex regions of elevated stiffness; (2) to handle noise levels inherent in typical instrumentation; and (3) to generate three-dimensional elasticity images. For our tests we utilize both synthetic and experimental displacement data, and consider both qualitative and quantitative measures of performance. We conclude that the method is robust and accurate, and a good candidate for clinical application because of its computational speed and efficiency..

Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm that sometimes follows breast cancer treatment. Clinically, both skin and subcutis are swollen. Edema is considered to be predominantly subcutaneous and of an even distribution. The purpose of this study was to quantify the degree and uniformity of skin and subcutis swelling around the forearms of women with BCRL. Ten women with BCRL were recruited. Both forearms were examined using 20 MHz ultrasound to visualize the skin and 7 MHz ultrasound to visualize the subcutis. Skin thickness was between the bottom of the entry-echo and the skin-subcutis boundary. Subcutis thickness was measured between the skin-subcutis boundary and the subcutis-muscle boundary. Both average skin thickness (1.97 +/- 1.00 mm) and average subcutis thickness (10.32 +/- 5.63 mm) were greater in the ipsilateral arm than in the contralateral arm (skin 1.12 +/- 0.14 mm, subcutis 5.58 +/- 2.04 mm, p < 0.01, t-test). The degree of increase in skin thickness did not vary around the arm (p > 0.05, ANOVA), while the degree of increase in subcutis thickness did vary (p < 0.05). Skin thickness correlated negatively with subcutis thickness in the contralateral arm, but correlated positively in the ipsilateral arm. The skin and subcutis are thickened in the ipsilateral arm of patients with BCRL. Skin thickness is increased uniformly around the arm and correlates strongly with the degree of swelling, while subcutis swelling varies. The measurement of skin thickness using ultrasound may form a useful clinical tool in the diagnosis of lymphedema and also aid further investigation of therapeutic techniques..

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..

.

A digest is provided of work carried out at t tie Institute of Cancer Research to develop freehand elastography and apply it to breast investigations. Topics covered include the development of freehand elastography and its relationship to other methods, a description of the system for off-line clinical evaluation of the freehand method, comparison of the physical performances of freehand and mechanical elastography, early clinical results on 70 breast tumours, real-time imaging, quantitative elastography and psychophysical aspects of the detection and assessment; of elastic lesions. Progress in developing this new medical imaging modality is occurring rapidly throughout the world and its future looks promising..

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..

We examine the inverse problem associated with quantitative elastic modulus imaging: given the equilibrium strain field in a 2D incompressible elastic material, determine the elastic stiffness (shear modulus). We show analytically that a direct formulation of the inverse problem has no unique solution unless stiffness information is known a priori on a sufficient portion of the boundary. This implies that relative stiffness images constructed on the assumption of constant boundary stiffness are in error, unless the stiffness is truly constant on the boundary. We show further that using displacement boundary conditions in the forward incompressible elasticity problem leads to a nonunique inverse problem. Indeed, we give examples in which exactly the same strain field results from different elastic modulus distributions under displacement boundary conditions. We also show that knowing the stress on the boundary can, in certain configurations, lead to a well-posed inverse problem for the elastic stiffness. These results indicate what data must be taken if the elastic modulus is to be reconstructed reliably and quantitatively from a strain image..

.

.

A prototype freehand elastographic imaging system has been developed for clinical breast imaging. The system consists of a fast data acquisition system, which is able to capture sequences of intermediate frequency echo frames at full frame rate from a commercial ultrasound scanner whilst the breast is deformed using hand-induced transducer motion. Two-dimensional echo tracking was used in combination with global distortion compensation and multi-compression averaging to minimise decorrelation noise incurred when stress is applied using hand-induced transducer motion. Experiments were conducted on gelatine phantoms to evaluate the quality of elastograms produced using the prototype system relative to those produced using mechanically induced transducer motion. The strain sensitivity and contrast-to-noise ratio of freehand elastograms compared favourably with elastograms produced using mechanically induced transducer motion. However, better dynamic range and signal-to-noise ratio was achieved when elastograms were created using mechanically induced transducer motion. Despite the loss in performance incurred when stress is applied using hand-induced transducer motion, it was concluded that the prototype system performed sufficiently well to warrant clinical evaluation..

.

.

This study documents the optical reflectance characteristics of pigmented skin lesions and evaluates their potential for improving the differential diagnosis of malignant melanoma from benign pigmented skin lesions. Optical reflectance spectra in the wavelength range 320-1100 nm were obtained from 121 lesions already selected by expert dermatologists as suspicious of malignancy. Characteristic differences in spectra from benign and malignant lesions were studied. Feature extraction showed significant differences between lesion groups classified by histology. Seven of the most relevant features were used in the discriminant analysis of reflectance spectra from 15 melanoma and 32 compound naevi which resulted in a sensitivity of 100% and specificity of 84.4% when compared with histology. This simple objective technique appears to perform as well as the expert dermatologist and may improve the diagnostic accuracy of non-specialists such as trainees and GPs. Further prospective clinical study of reflectance spectrophotometry in a larger patient group is now required..

This paper describes an inverse reconstruction technique based on a modified Newton Raphson iterative scheme and the finite element method, which has been developed for computing the spatial distribution of Young's modulus from within soft tissues. Computer simulations were conducted to determine the relative merits of reconstructing tissue elasticity using knowledge of (a) known displacement boundary conditions (DBC), and (b) known stress boundary conditions (SBC). The results demonstrated that computing Young's modulus using knowledge of SBC allows accurate quantification of Young's modulus. However, the quality of the images produced using this reconstruction approach was dependent on the Young's modulus distribution assumed at the start of the reconstruction procedure. Computing Young's modulus from known DBC provided relative estimates of tissue elasticity which, despite the disadvantage of not being able to accurately quantify Young's modulus, formed images that were generally superior in quality to those produced using the known SBC, and were not affected by the trial solution. The results of preliminary experiments on phantoms demonstrated that this reconstruction technique is capable in practice of improving the fidelity of tissue elasticity images, reducing the artefacts otherwise present in strain images, and recovering Young's modulus images that possess excellent spatial and contrast resolution..

.

There are potential clinical benefits if non-invasive methods can be used to diagnose or exclude melanoma..

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 Young's 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. Young's 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 (Young's 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..

Successful treatment of skin cancer, especially melanoma, depends on early detection, but diagnostic accuracy, even by experts, can be as low as 56% so there is an urgent need for a simple, accurate, non-invasive diagnostic tool. In this paper we have compared the performance of an artificial neural network (ANN) and multivariate discriminant analysis (MDA) for the classification of optical reflectance spectra (320 to 1100 nm) from malignant melanoma and benign naevi. The ANN was significantly better than MDA, especially when a larger data set was used, where the classification accuracy was 86.7% for ANN and 72.0% for MDA (p < 0.001). ANN was better at learning new cases than MDA for this particular classification task. This study has confirmed that the convenience of ANNs could lead to the medical community and patients benefiting from the improved diagnostic performance which can be achieved by objective measurement of pigmented skin lesions using spectrophotometry..

.

.

.

We report our initial experience with segmented color Doppler velocity-based estimates of tumor vascularity for various histogically proven soft-tissue masses..

.

.

.

.

.

.

To evaluate the effects of a new microbubble contrast agent for ultrasound (US) on breast masses..

PURPOSE: To evaluate the effects of a new microbubble contrast agent for ultrasound (US) on breast masses.MATERIALS AND METHODS: Thirty-four patients underwent color Doppler US before and after intravenous injection of a ''contrast agent'' containing microbubbles. The authors subjectively evaluated the increase in intensity of the Doppler signals, the changes in the vascular patterns, and the timing of the transit of the microbubble bolus. The diagnostic confidence was assessed before and after administration of contrast material.RESULTS: After contrast material injection, there was greater and longer signal enhancement in the cancers than in the benign lesions. The cancers displayed characteristic vascular morphologic features, with more additional vessels visualized in relation to the lesion and a greater increase in vascular tortuousity. Shunts between vessels were demonstrated in all cancers but were not seen in any benign lesion. The diagnostic confidence increased with use of the contrast agent. The appearance at contrast-enhanced US led to a change in the US diagnosis in four patients. This increased both sensitivity and specificity to 100%.CONCLUSION: Injection of a microbubble agent enabled accurate differentiation of benign masses from carcinomas..

.

Adaptive speckle reduction could mask diagnostic features and adversely affect diagnosis of focal breast lesions. Four radiologists assessed focal breast lesions (29 malignant and 31 benign) by blind review of representative static B-mode scans before and after adaptive speckle reduction processing, scoring 14 diagnostic features for breast cancer and recording their opinions on the diagnosis and on how adaptive speckle reduction affected interpretation of each feature. No adverse affect on diagnosis of malignant (P = 0.756) or benign (P = 1.000) breast lesions was found, despite some differences in scoring of the diagnostic features after adaptive speckle reduction. Observer recognition of most diagnostic features was easier after adaptive speckle reduction (e.g., edge definition [50% of cases], edge regularity [40%], lesion texture [44%], and lesion echogenicity [35%])..

To quantify color Doppler (CD) signals reflected by breast lesions to improve differential diagnosis and serial comparisons..

A technique has been developed to segment (separate), from a digitized colour Doppler video image, the colour and greyscale information and then to estimate from the colour information the original mean Doppler frequency shift data from which the image was created. The remapped velocity image is then analysed to extract numerical features of the tumour vasculature. The present version of the software is set-up to work for an Acuson 128 colour Doppler system using the V4 colour scale, although it should work well with any system which modulates only two colours for each flow direction and displays a colour calibration scale at the side of the image. Accuracy of classification of greyscale, colour and flow direction was estimated as being in the region of 95% for typical breast tumour images. The degree of agreement between the remapped colour velocity values and those stated by the scanner at the same image locations was evaluated in terms of the linearity of the relationship (> 99%), precision (better than +/- 5%) and accuracy (better than 7.6%). We investigated the value, for diagnosis and assessment of response of, a variety of characteristics of the displayed vascularity. At present, the software calculates the following vascular image features within any region of interest defined by the operator: mean displayed velocity, maximum displayed velocity, standard deviation of displayed velocity, total area occupied by colour signal, percentage area occupied by colour signal, area integral of displayed velocity and the total displayed velocity per unit area..

An automated system for measuring features of colour Doppler (CD) images has been examined for its ability to measure tissue perfusion in vivo under conditions of diffuse vascularity. Seven statistical features were extracted from CD images of human calf muscle and compared with the arterial input measured by plethysmography. It was found that, when appropriate scanning procedures are employed, good correlation is achieved with arterial input (r = 0.96 to 0.99). Ultrasound beam angle was important, even for the assessment of "colour area." A sensitive velocity scale was ideal for "percentage colour" (r = 0.979). "Mean colour velocity" correlates well with arterial input (r = 0.979) when the volocity scale was optimised for each CD scan. "Integrated colour velocity per unit area" was more responsive when using a variable velocity scale (r = 0.99) than a fixed velocity scale (r = 0.98), but was less responsive to low flow. Automated CD analysis speeds up the process of quantitative assessment of tissue vasculature and perfusion. It is therefore essential for the analysis of dynamic studies of ultrasound contrast agents and serial examinations when monitoring response to therapy..

Eight human skin samples were excised postmortem from the upper and lower back, chest and abdomen from two cadavers. The acoustical speed, attenuation and backscatter were measured as a function of frequency (20 to 30 MHz) at 100 positions on a uniform grid over a cross-sectional slice through each sample with the sound incident in a direction parallel to the skin surface. Measurements were made at 24 +/- 0.5 degrees C. Samples were then frozen, cut and stained for histological examination and quantification of fibrous proteins and fat content. The mean attenuation coefficients obtained for whole skin agreed well with previously published results. Employing the model alpha = alpha 1f" where alpha is the attenuation coefficient in decibels per centimeter, alpha 1 is the value of the attenuation coefficient at 1 MHz and f is frequency raised to the power n, mean values (+/- 1 standard deviation) for epidermis were alpha 1 = 0.44 +/- 0.26 and n = 1.55 +/- 0.12, and for dermis alpha 1 = 0.264 +/- 0.17 dB cm-1 and n = 1.69 +/- 0.084. Using a similar model the mean backscatter coefficient was defined by mu 1 = (5.01 +/- 25.76) x 10(-8) Sr-1 cm-1, n = 3.77 +/- 1.5 for the epidermis, and mu 1 = (1.79 +/- 19.5) x 10(-6) and n = 2.76 +/- 1.4 for the dermis. The speed of sound values fell within the range to be found in the literature with a mean value in the epidermis of 1645 m s-1 and in the dermis of 1595 m s-1. Significant, strong correlation existed between the spatially averaged fibrous protein content in the epidermis and dermis and the spatially averaged integrated attenuation measurements. Likewise, strong correlation existed between integrated backscatter and fibrous protein content in the epidermis but not in the dermis. Further research is required to confirm these preliminary findings and to evaluate the role of collagen fibre orientation as a source of variation in the backscattering coefficient of dermis..

To assess the ability of color Doppler flow imaging to help evaluate the response of breast cancer to medical therapy..

Sixteen skin tumours and one BCG vaccination granuloma were examined by 20-MHz B-scan ultrasound. Images were compared with closely matched histological sections of excised lesions. The correlation between histology and ultrasound was excellent for maximum tumour depth measurements (r = 0.96, P < 0.0001), but less good for maximum width (r = 0.84, P < 0.0001) because of the elastic contraction of tissue at excision. Architectural detail of lesions on histological sections corresponded well with that on ultrasound images. There was a good correlation for heterogeneity (collagen distribution vs. echo pattern (r = 0.86, P < 0.0001)), and between collagen content and echogenicity of lesions (r = 0.69, P < 0.003). Strong correlations were also obtained for echogenicity vs. spacing of collagen bundles (r = -0.65, P < 0.005), echogenicity vs. collagen bundle size (r = 0.58, P < 0.02), and echogenicity vs. cellularity (r = -0.68, P < 0.003). Results for dermatofibroma were atypical, due to paradoxical low internal echogenicity and increased echo absorption. B-scanning is a reliable non-invasive method for assessing tumour dimensions, and has potential for the study of tumour characteristics for diagnostic purposes..

To subjectively and semiquantitatively evaluate color Doppler signals on images of breast lesions..

Methods for quantitative imaging of ultrasound propagation properties were applied to the examination of the acoustic appearance of lesions generated by high intensity focused ultrasound in excised pig livers. Single lesions, about 10 mm maximum diameter by 30 mm long, were created in each of six liver specimens. Two dimensional images (32 by 32 points) of sound speed, mean attenuation coefficient (as a function of frequency in the range 3 to 8.5 MHz) and mean backscattering coefficient (5 to 8 MHz) were obtained in 7 mm thick sections of tissue, cut to include a cross-section through the lesion. Images of these properties, presented alongside surface photographs of the samples, provided a qualitative demonstration that attenuation coefficient was the most useful and backscattering coefficient was the least useful acoustic parameter for visualizing such lesions. Quantitatively the data demonstrated significant increases in attenuation coefficient and sound speed in lesioned liver relative to normal, whereas backscattering was shown not to change in a significant manner except when undissolved gas is the mechanism for increased acoustic scattering. Samples where gas was not fully removed following lesion production gave significant increases in backscattering at the lesion centre, but the shape and size of regions of high backscattering coefficient corresponded poorly with the shape and size of the lesions, unlike attenuation and sound speed for which such correspondence was good..

A systematic method to compensate for nonlinear amplification of individual ultrasound B-scanners has been investigated in order to optimise performance of an adaptive speckle reduction (ASR) filter for a wide range of clinical ultrasonic imaging equipment. Three potential methods have been investigated: (1) a method involving an appropriate selection of the speckle recognition feature was successful when the scanner signal processing executes simple logarithmic compressions; (2) an inverse transform (decompression) of the B-mode image was effective in correcting for the measured characteristics of image data compression when the algorithm was implemented in full floating point arithmetic; (3) characterising the behaviour of the statistical speckle recognition feature under conditions of speckle noise was found to be the method of choice for implementation of the adaptive speckle reduction algorithm in limited precision integer arithmetic. In this example, the statistical features of variance and mean were investigated. The third method may be implemented on commercially available fast image processing hardware and is also better suited for transfer into dedicated hardware to facilitate real-time adaptive speckle reduction. A systematic method is described for obtaining ASR calibration data from B-mode images of a speckle producing phantom..

Adaptive speckle reduction, which is designed to improve image contrast, dramatically alters the familiar appearance of the ultrasonographic B-mode scan. The acceptability to radiologists of this alternative method of display was assessed. Four experienced radiologists selected B-mode scans from 83 liver and 71 breast examinations and graded the change in diagnostically important features after adaptive speckle reduction. There was no loss of important anatomic detail in the smoothed images and a net reduction in image artifacts. Removal of speckle noise improved definition of lesion margins in 38.3% of cases and enhanced visibility of metastases in 35.4% of liver studies and 7.7% of breast lesions. In 42.1% of cases, the textural information in the image was judged to be enhanced. Image information in general was said to be better seen in 49.5% of cases. The preliminary radiologic experience with speckle-reduced B-mode echograms is favorable and does not indicate generation of any substantial image artifacts..

Early experiences of new forms of adaptive filtering for ultrasound speckle reduction and parametric imaging, using off-line conventional digital processing, have been sufficiently encouraging to warrant examining the feasibility of implementing specific algorithms in real-time. A hardware two-dimensional real-time filter is described which consists of a hybrid digital/analogues system in which the video signal from any scanner is sampled to 256 points per line and passed sequentially through a series of shift registers, in order to derive a 5 x 5 window of values which surrounds the image point currently being processed. These 25 video signals are then used as inputs to an analogue processor, which provides the filtered output. The real-time processed images show clear evidence of speckle smoothing without blurring of tissue structural information but possess limited pixel resolution..

A new coaxial needle, containing a retractable anchoring wire with a helical tip, has been developed for purposes of mammographic and sonographic localization of non-palpable suspicious breast abnormalities before surgical excision. The helically shaped tip provides the needle with a number of potential advantages over other currently available localization needles. During in vitro comparisons with other needles quantitative and qualitative evidence was obtained to suggest that the new needle can be expected to have improved anchoring capability, be deflected less by tough fibrous tissue interfaces and be more visible sonographically. The anchoring wire can also be retracted and repositioned. Preliminary clinical experience with the needle was consistent with these expectations..

We review the current state of knowledge of the processes by which the information content of ultrasonic pulse-echo images is transferred to an observer, to the point of contributing to diagnostic judgments. As systematic knowledge in this specific field is rather sparse, we present relevant information and techniques derived from other areas of image science, both medical and otherwise. Quantitative measures both of the information content of ultrasonic and other images and of their characteristic noise content are first considered. An account is then given of the relevant aspects of human visual psychophysics, with particular reference to perception of contrast and detail, image texture, movement and colour, again with emphasis on documenting quantitative aspects of such behaviour. Against this background, we consider the efficiency, in current practice, of image information transfer to a human observer, how and to what extent this could be improved by changes in practice and, in particular, in what situations substantial innovations in machine processing of image data would be expected to improve human performance. It is suggested that several problems in the field may provide a worthwhile and challenging scope for future research..

The color Doppler signals in 60 patients with breast masses were assessed subjectively, and a regional grading method was developed for quantitation of displayed blood vessel density. Among 21 patients with breast carcinoma, moderate or high flow was demonstrated in all but one, with an average of 0.5 vessels per square centimeter and color pixels occupying 12.2% of the image area. Among 33 patients with benign disorders, no flow was demonstrated in 25 and slight to moderate flow was seen in five, with an average of 0.01 vessels per square centimeter, occupying 0.8% of the image area. Cancers as small as 10 mm in diameter were positive for flow. High-velocity flow was seen only in malignancies; it was observed in four cases and may have been due to arteriovenous shunting. Flow was less readily detected in recurrent tumors; two of seven tumors were weakly positive. Color Doppler shows promise as an adjunct to ultrasound imaging in the differential diagnosis of breast lesions..

For the purpose of assessing and comparing the practical performance of various specific approaches to quantitative tissue characterisation, three sets of performance criteria are proposed, relating respectively to contrast resolution, spatial resolution, and speed of presentation. In each case numerical performance targets are suggested: in particular that spatial resolution should preferably be within a linear factor of three of the best achievable anatomical resolution of the associated imaging techniques and that presentation speed should be 'real time' (i.e. about 10 Hz). In the light of these criteria and performance targets the main existing approaches to ultrasonic tissue characterisation are then considered. These are classified in two groups: first those approaches based on measurements of bulk properties of tissues and secondly those related to parameters of the structural organisation of tissues. Examination of available evidence suggests that the latter group are more promising than the former. Finally it is argued that ultrasonic methods of tissue characterisation have substantial practical potential but that the realisation of such potential is contingent on achieving consensus on choice of a single, optimised and generally applicable approach that would carry with it the linked benefits of industrial standardisation and broad sharing of clinical experience..

Speckle is prominent on all cross sectional echocardiograms. In order to assess its effects on image quantification, frames from a sector scanner with a six bit grey scale were stored and processed off line to identify and smooth the speckle by means of an adaptive filter based on fully developed speckle. In 14 controls, 12 patients with hypertrophic cardiomyopathy, and 12 with secondary left ventricular hypertrophy, filtering significantly reduced the standard deviation of echo intensity, which was used as a measure of the scatter of pixel amplitude, in all three groups (by 52%, 46%, and 46% respectively). The mean value of back-scattered echo intensity itself, however, was reduced by only 7%, 5%, and 8% respectively, and median values were not affected at all. Mean (SD) left ventricular cavity areas on the apical four chamber view were significantly increased from 26 (15) to 30 (17) cm2. The valve dimensions in the parasternal minor axis in 10 patients with mitral stenosis were significantly increased by 11% laterally, but were unaffected anteroposteriorly. Subjective image quality was appreciably modified: endocardial boundaries in apical views were enhanced and the septal "ground glass" appearance was lost in hypertrophic cardiomyopathy. Speckle reduction therefore greatly reduced the scatter of pixel values, with little effect on the mean regional back scattered echo amplitude. It also modified the perceived image texture. Improved boundary definition consistently increased the area estimates, particularly when these depended on lateral rather than range resolution..

.

.

.

.

.

.

Semi-quantitative diagnostic features were extracted by a visual analysis of the echographic images of selected cases of breast disease and the results stored in a computer database. The long term aim is to create an environment suitable for the use of multivariate statistical methods systematically to evaluate ultrasound interpretive criteria and diagnostic performance in relation to factors such as scanning instrumentation and other diagnostic techniques. Eventually it is hoped that it will be possible to generate a system for computer assisted diagnosis and training. The results of this pilot study serve to demonstrate the feasibility of the approach and a univariate analysis is used to provide a preliminary ranking of diagnostic features. Features found to be particularly valuable for distinguishing benign from malignant solid lesions were the regularity and definition of the edge of the tumour, the mobility of the tumour and measures of echo heterogeneity within and posterior to the tumour mass..

An analysis is made of the kinetics of human liver parenchyma in response to mechanical impulses arising in the heart and aorta, and the results are applied to predicting the time course of the correlation between two time-separated A-scans derived from various regions of the liver. Such predictions are found to correspond well with data derived clinically, both from volunteers and from patients with liver metastases, using a commercial, real-time sector scanner. On the basis of Fourier spectral features of the clinically derived correlation patterns, a clear quantitative separation was demonstrated between the kinetic response of three classes of tissue: normal liver in volunteers, metastatic deposits in liver of cancer patients, and histologically normal liver regions in the same patients..

.

.

The breasts of seven normal female volunteers were examined using a continuous wave, directional 10 MHz ultrasonic Doppler system. A range of quantitative features were extracted from recorded Doppler signals by first computing an average, single cardiac cycle sonogram from 4-6 overlayed cardiac cycles of sonogram data taken from each recording. Substantial variations were observed to occur in both frequency and amplitude characteristics of the Doppler signals during the menstrual cycle and pregnancy. For each subject the two breasts behaved similarly and the fluctuations correlated with known variations in blood hormone levels and breast surface temperature. In the one case of pregnancy, the mammary blood flow appeared to increase throughout pregnancy, beginning very shortly after conception. It is concluded that the normal fluctuations of the blood flow in the breast may make a large contribution to the variance of Doppler-derived blood flow features for the pre-menopausal breast. Use of the contralateral breast as a control is advocated for studies of the application of the Doppler method to the diagnosis and measurement of therapeutic response of breast cancer in young women. The usefulness of the contralateral breast as such a control might be enhanced by performing Doppler examinations only at about the midcycle. If the presence of a tumour were to alter these fluctuations there may be a possibility of using the effect to advantage alongside other methods for early diagnosis of breast cancer..

.

.

.

.

Current medical ultrasonic scanning instrumentation permits the display of fine image detail (speckle) which does not transfer useful information but degrades the apparent low contrast resolution in the image. An adaptive two-dimensional filter has been developed which uses local features of image texture to recognize and maximally low-pass filter those parts of the image which correspond to fully developed speckle, while substantially preserving information associated with resolved-object structure. A first implementation of the filter is described which uses the ratio of the local variance and the local mean as the speckle recognition feature. Preliminary results of applying this form of display processing to medical ultrasound images are very encouraging; it appears that the visual perception of features such as small discrete structures, subtle fluctuations in mean echo level and changes in image texture may be enhanced relative to that for unprocessed images..

.

Tumour growth delay has been investigated as an endpoint of radiation effect in selected patients with superficial metastases measured by calipers and ultrasound. Of 42 patients referred for study with two or more nodules, 17 were suitable for entry into protocols evaluating single or multifraction treatment. The reproducibility of tumour growth delay to the same dose schedule was evaluable in four patients and the sensitivity to 10-20% differences in total dose was evaluable in three patients. No significant size dependency was detected in the response of nodules to radiotherapy and the findings suggest that the growth delay endpoint is sensitive to 20% differences in radiation dose. Evaluable patients with multiple measurable nodules are uncommon but constitute a valuable resource for the testing of biological response modifiers, including radiosensitizers..

.

.

.

.

.

.

.

A method is described for quantifying tissue movement in vivo from the computation of correlation coefficient between pairs of A-scans with appropriate time separation. The method yields quantifiable and repeatable secondary patterns of soft tissue movement in response to primary cardiac movement in a given subject, shows consistently different results as between normal livers and a variety of abdominal tumours, and is sensitive to either progress or therapeutically-induced regression of malignant disease. While the results reported here have been obtained using somewhat simple and crude equipment, the method is well suited to implementation on a commercial real-time scanner..

The greatest variation in published data of the attenuation of ultrasound in mammalian liver in vitro occurs at the lower end of the 0.5 to 7 MHz frequency range and gives rise to some departure from a linear or simple power law dependence of attenuation on frequency. These effects do not appear to be highly dependent on the method of measurement. It is suggested that they are due to a varying presence of small gas bubbles distributed throughout the tissue--a suggestion based on calculated estimates of the attenuation due to microscopic bubbles and on the measured frequency dependence of attenuation in water loaded sponges containing varying amounts and distribution of gas. We now believe that preferred methods of tissue specimen preparation, for in vitro measurement of ultrasonic attenuation or scattering, should involve either pressurization as described elsewhere (Frizzell et al., 1979) or storage under refrigeration..

.

.

.

.

.

.

A 10 MHz, continuous wave ultrasonic Doppler system was used to study the blood flow associated with normal and malignant mammary tissue in patients with breast cancer. Some patients were receiving endocrine therapy and were examined repeatedly over a period of months. each of 6 characteristics extracted from the time varying maximum Doppler-shift frequency were averaged over signals obtained from a number of sites in the vicinity of the tumour, and from corresponding sites in the normal breast. A method was devised to allow location of previously examined vessels for subsequent examinations. The preliminary results of analysing approx. 400 recordings of Doppler signals obtained from 16 patients (6 of whom received endocrine therapy) are presented. The most informative of the 6 characteristics were the maximum systolic frequency (A) and the "mean" frequency (M) (= A + B/2 where B is the maximum frequency during end diastole). The average values of A and M obtained from the tumourous breast were always greater than those obtained from the normal breast in the same patient. A and M were roughly proportional to tumour volume, with extrapolated values at zero volume only slightly greater than the corresponding mean values for normal breast tissue. On average, changes in the values of A and M obtained from tumour sites during endocrine therapy appeared to occur in association with, and possibly slightly in advance of, changes in the tumour volume..

.

.

.

.

.

.

A method has been developed which can predict the appearance and properties of B-scan images. The theoretical basis for the tissue models used, and the assumptions made in the simulation concerning the nature of pulse-echo imaging, are discussed. A key feature of the simulation is the Fourier domain synthesis of the tissue model, which permits convenient specification of some statistical properties of a randomly inhomogeneous scattering medium. Other characteristics that may be specified include the ultrasonic pulse and beam shapes, and subsequent signal processing. Both the initial tissue model and the simulated B-scan image are displayed as grey-scale pictures, allowing visual comparison in the same way that clinical B-scans are currently observed. Preliminary results of applying the simulation are shown to have a number of features in common with clinical images and with scans of a test object. A better understanding of the nature of pulse-echo images is gained and conclusions drawn regarding the range of system and tissue parameters over which these images convey information about the tissue structure. The method may also be of use to determine optimum design of equipment for imaging and tissue characterisation, and to investigate the extent to which the acoustic structure of tissues can be described in terms of simple mathematical models..

.

.

.

.

.

.

.

.

.

.

.

.

.

.

The purpose of this study was to establish interobserver reproducibility of Young's modulus (YM) derived from ultrasound shear wave elastography (US-SWE) in the normal prostate and correlate it with multiparametric magnetic resonance imaging (mpMRI) tissue characteristics. Twenty men being screened for prostate cancer underwent same-day US-SWE (10 done by two blinded, newly-trained observers) and mpMRI followed by 12-core biopsy. Bland-Altman plots established limits of agreement for YM. Quantitative data from the peripheral zone (PZ) and the transitional zone (TZ) for YM, apparent diffusion coefficient (ADC, mm2/s from diffusion-weighted MRI), and Ktrans (volume transfer coefficient, min-1), Ve (extravascular-extracellular space, %), Kep (rate constant, /min), and initial area under the gadolinium concentration curve (IAUGC60, mmol/L/s) from dynamic contrast-enhanced MRI were obtained for slice-matched prostate sextants. Interobserver intraclass correlation coefficients were fair to good for individual regions (PZ = 0.57, TZ = 0.65) and for whole gland 0.67, (increasing to 0.81 when corrected for systematic observer bias). In the PZ, there were weak negative correlations between YM and ADC ( p = 0.008), and Ve ( p = 0.01) and a weak positive correlation with Kep ( p = 0.003). No significant intermodality correlations were seen in the TZ. Transrectal prostate US-SWE done without controlling manually applied probe pressure has fair/good interobserver reproducibility in inexperienced observers with potential to improve this to excellent by standardization of probe contact pressure. Within the PZ, increase in tissue stiffness is associated with reduced extracellular water (decreased ADC) and space (reduced Ve)..

.

.

.

.

.

.

.