Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: a pilot study.

AIMS: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. MATERIALS AND METHODS: Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. RESULTS: The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements CONCLUSIONS: Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.

Three-dimensional ultrasound imaging.

This review is about the development of three-dimensional (3D) ultrasonic medical imaging, how it works, and where its future lies. It assumes knowledge of two-dimensional (2D) ultrasound, which is covered elsewhere in this issue. The three main ways in which 3D ultrasound may be acquired are described: the mechanically swept 3D probe, the 2D transducer array that can acquire intrinsically 3D data, and the freehand 3D ultrasound. This provides an appreciation of the constraints implicit in each of these approaches together with their strengths and weaknesses. Then some of the techniques that are used for processing the 3D data and the way this can lead to information of clinical value are discussed. A table is provided to show the range of clinical applications reported in the literature. Finally, the discussion relating to the technology and its clinical applications to explain why 3D ultrasound has been relatively slow to be adopted in routine clinics is drawn together and the issues that will govern its development in the future explored.

Quantitative 3D imaging parameters improve prediction of hip osteoarthritis outcome.

Osteoarthritis is an increasingly important health problem for which the main treatment remains joint replacement. Therapy developments have been hampered by a lack of biomarkers that can reliably predict disease, while 2D radiographs interpreted by human observers are still the gold standard for clinical trial imaging assessment. We propose a 3D approach using computed tomography-a fast, readily available clinical technique-that can be applied in the assessment of osteoarthritis using a new quantitative 3D analysis technique called joint space mapping (JSM). We demonstrate the application of JSM at the hip in 263 healthy older adults from the AGES-Reykjavík cohort, examining relationships between 3D joint space width, 3D joint shape, and future joint replacement. Using JSM, statistical shape modelling, and statistical parametric mapping, we show an 18% improvement in prediction of joint replacement using 3D metrics combined with radiographic Kellgren & Lawrence grade (AUC 0.86) over the existing 2D FDA-approved gold standard of minimum 2D joint space width (AUC 0.73). We also show that assessment of joint asymmetry can reveal significant differences between individuals destined for joint replacement versus controls at regions of the joint that are not captured by radiographs. This technique is immediately implementable with standard imaging technologies.

Measurement of the bone endocortical region using clinical CT.

The extent of the endocortical region and cortical bone mineral density (cBMD) throughout the proximal femur are of interest as both have been linked to fracture risk and osteoporosis treatment response. Non-invasive in-vivo clinical CT-based techniques capable of measuring the cortical bone attributes of thickness, density and mass over a bone surface have already been proposed. Several studies have robustly shown these methods to be capable of producing cortical thickness measurements to a sub-millimetre accuracy. Unfortunately, these methods are unable to provide high quality cBMD estimates, and are not designed to measure any attributes over the endocortical region of cortical bone. In this paper, we develop a cortical bone mapping based technique capable of providing an improved cBMD estimate and a measure of the endocortical width, while maintaining similar quality cortical thickness and trabecular bone mineral density (tBMD) estimates. The performance of the technique was assessed using a paired dataset of ex-vivo QCT and HR-pQCT scans across 72 proximal femurs. The HR-pQCT scans were analysed using a new method developed for this study: high resolution tissue classification (HRTC). In HRTC the cortical, endocortical and sub-surface trabecular bone features are extracted from the partially resolvable microarchitectural details in the HR-pQCT scan. We demonstrate that measurement of the endocortical extent from QCT is possible with an accuracy of -0.15±0.71mm, and that local cBMD can be measured down to densities of 300 mg/cm3.

How does the femoral cortex depend on bone shape? A methodology for the joint analysis of surface texture and shape.

In humans, there is clear evidence of an association between hip fracture risk and femoral neck bone mineral density, and some evidence of an association between fracture risk and the shape of the proximal femur. Here, we investigate whether the femoral cortex plays a role in these associations: do particular morphologies predispose to weaker cortices? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm2) in a cohort of 125 females. Principal component analysis of the femoral surfaces identified three modes of shape variation accounting for 65% of the population variance. We then used statistical parametric mapping (SPM) to locate regions of the cortex where CMSD depends on shape, allowing for age. Our principal findings were increased CMSD with increased gracility over much of the proximal femur; and decreased CMSD at the superior femoral neck, coupled with increased CMSD at the calcar femorale, with increasing neck-shaft angle. In obtaining these results, we studied the role of spatial normalization in SPM, identifying systematic misregistration as a major impediment to the joint analysis of CMSD and shape. Through a series of experiments on synthetic data, we evaluated a number of registration methods for spatial normalization, concluding that only those predicated on an explicit set of homologous landmarks are suitable for this kind of analysis. The emergent methodology amounts to an extension of Geometric Morphometric Image Analysis to the domain of textured surfaces, alongside a protocol for labelling homologous landmarks in clinical CT scans of the human proximal femur.

A new quantitative 3D approach to imaging of structural joint disease.

Imaging of joints with 2D radiography has not been able to detect therapeutic success in research trials while 3D imaging, used regularly in the clinic, has not been approved for this purpose. We present a new 3D approach to this challenge called joint space mapping (JSM) that measures joint space width in 3D from standard clinical computed tomography (CT) data, demonstrating its analysis steps, technical validation, and reproducibility. Using high resolution peripheral quantitative CT as gold standard, we show a marginal over-estimation in accuracy of +0.13 mm and precision of ±0.32 mm. Inter-operator reproducibility bias was near-zero at -0.03 mm with limits of agreement ±0.29 mm and a root mean square coefficient of variation 7.5%. In a technical advance, we present results from across the hip joint in 3D with optimum validation and reproducibility metrics shown at inner joint regions. We also show JSM versatility using different imaging data sets and discuss potential applications. This 3D mapping approach provides information with greater sensitivity than reported for current radiographic methods that could result in improved patient stratification and treatment monitoring.

Novel three-dimensional bone 'mapping' software can help assess progression of osseous metastases from routine CT.

Imaging of bone metastasis response to therapy is a research priority. Stradwin is a new software-tool, with demonstrated sub-voxel accuracy in assessing cortical bone properties from routine CT. We applied this technology to the context of osseous metastases, with particular focus on disease progression using prostate cancer as a model. 3D-rendered 'bone-maps' were produced for 20 men with advanced prostate cancer, including a sub-cohort of 9 who had undergone serial scans. Correlation between baseline interpretation and assessments of progression between modalities was assessed. Bone-maps took significantly less time to interpret than CT bone windows (P < 0.001). Initial bone-mapping, without adjustment, demonstrated sensitivity and specificity for suspicious areas on CT of 70.7% and 73.1% respectively. Evaluating disease over time, concordance between bone-maps and current practice using RECIST outcomes was 100%.This study demonstrates the feasibility and potential use of this free post-processing software in the serial assessment of osseous metastases.

3D reconstruction of the skeletal anatomy of the normal neonatal foot using 3D ultrasound.

Currently imaging plays a limited role in the assessment of the neonate with a foot deformity. The aim of this study was to establish a technique for examining the neonatal foot with three-dimensional ultrasound (3D US). 3D US was attempted on the normal feet of 20 infants (9 male, 11 female) under 6 weeks old (range 35-41 days). The data sets were obtained whilst the infants were feeding or asleep to minimize movement artefact. A high-resolution optically tracked freehand 3D US system (Diasus, 16 MHz transducer) was used with Stradx software to acquire and analyse the data sets. Manual segmentation of the non-ossified tarsi from the data sets was performed. Five infants were too restless to be examined. 107 data sets were recorded from 22 feet of the remaining 15 infants. 21 of the data sets were discarded due to movement artefact. 86 were suitable for manual segmentation. Surface interpolation of the segmented data sets produced surface rendered reconstructions illustrating the complex 3D anatomy of the foot. This new technique may offer a method of examining the deformed foot, e.g. congenital talipes equinovarus.

Spatial mapping of the brachial plexus using three-dimensional ultrasound.

Imaging of the brachial plexus with MRI and standard two-dimensional (2D) ultrasound has been reported, and 2D ultrasound-guided regional anaesthetic block is an established technique. The aim of this study was to map the orientation of the brachial plexus in relation to the first rib, carotid and subclavian arteries, using three-dimensional (3D) ultrasound. A free-hand optically tracked 3D ultrasound system was used with a 12 MHz transducer. 10 healthy volunteers underwent 3D ultrasound of the neck. From the 3D ultrasound data sets, the outlines of the brachial plexus, subclavian artery and first rib were manually segmented. A surface was interpolated from the series of outlines to produce a spatially orientated 3D reconstruction of the brachial plexus. The brachial plexus could be mapped in all volunteers, although a variation in image resolution between individuals existed. Anatomical variations were demonstrated between the 10 volunteers; the most notable and clinically relevant was the alignment of the plexus divisions. 3D reconstructions illustrated the plexus, changing its orientation from a vertical alignment in the interscalene region to a more horizontal alignment in the supraclavicular fossa. Spatial mapping of the brachial plexus is possible with 3D ultrasound using the subclavian artery and first rib as landmarks. There is a deviation from the conventionally described anatomy and this may have implications for the administration of regional anaesthesia.

Independent measurement of femoral cortical thickness and cortical bone density using clinical CT.

The local structure of the proximal femoral cortex is of interest since both fracture risk, and the effects of various interventions aimed at reducing that risk, are associated with cortical properties focused in particular regions rather than dispersed over the whole bone. Much of the femoral cortex is less than 3mm thick, appearing so blurred in clinical CT that its actual density is not apparent in the data, and neither thresholding nor full-width half-maximum techniques are capable of determining its width. Our previous work on cortical bone mapping showed how to produce more accurate estimates of cortical thickness by assuming a fixed value of the cortical density for each hip. However, although cortical density varies much less over the proximal femur than thickness, what little variation there is leads to errors in thickness measurement. In this paper, we develop the cortical bone mapping technique by exploiting local estimates of imaging blur to correct the global density estimate, thus providing a local density estimate as well as more accurate estimates of thickness. We also consider measurement of cortical mass surface density and the density of trabecular bone immediately adjacent to the cortex. Performance is assessed with ex vivo clinical QCT scans of proximal femurs, with true values derived from high resolution HRpQCT scans of the same bones. We demonstrate superior estimation of thickness than is possible with alternative techniques (accuracy 0.12 ± 0.39 mm for cortices in the range 1-3mm), and that local cortical density estimation is feasible for densities >800 mg/cm(3).

Association between femur size and a focal defect of the superior femoral neck.

Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk.

Surface interpolation from sparse cross sections using region correspondence.

The ability to estimate a surface from a set of cross sections allows calculation of the enclosed volume and the display of the surface in three-dimensions. This process has increasingly been used to derive useful information from medical data. However, extracting the cross sections (segmenting) can be very difficult, and automatic segmentation methods are not sufficiently robust to handle all situations. Hence, it is an advantage if the surface reconstruction algorithm can work effectively on a small number of cross sections. In addition, cross sections of medical data are often quite complex. Shape-based interpolation is a simple and elegant solution to this problem, although it has known limitations when handling complex shapes. In this paper, the shape-based interpolation paradigm is extended to interpolate a surface through sparse, complex cross sections, providing a significant improvement over our previously published maximal disc-guided interpolation. The performance of this algorithm is demonstrated on various types of medical data (X-ray computed tomography, magnetic resonance imaging and three-dimensional ultrasound). Although the correspondence problem in general remains unsolved, it is demonstrated that correct surfaces can be estimated from a limited amount of real data, through the use of region rather than object correspondence.

Correction of probe pressure artifacts in freehand 3D ultrasound.

We present an algorithm which combines non-rigid image-based registration and conventional position sensing to correct probe-pressure-induced registration errors in freehand three-dimensional (3D) ultrasound volumes. The local accuracy of image-based registration enables the accurate freehand acquisition of high resolution (>15 MHz) 3D ultrasound data, opening the way for 3D musculoskeletal examinations. External position sensor readings guarantee the large-scale positional accuracy of the data. Pressure correction is shown to dramatically increase the perceived quality of extended-field-of-view data sets and reslices through volumetric data sets, while quantitative comparisons of multiple in vivo volumes demonstrate the superior precision of the corrected data.

Fast surface and volume estimation from non-parallel cross-sections, for freehand three-dimensional ultrasound.

Volume measurements from ultrasound B-scans are useful in many clinical areas. It has been demonstrated previously that using three-dimensional (3-D) ultrasound can greatly increase the accuracy of these measurements. Freehand 3-D ultrasound allows freedom of movement in scanning, but the processing is complicated by having non-parallel scan planes. Two techniques are proposed for volume measurement from such data, which also improve surface and volume estimation from data acquired on parallel planes. Cubic planimetry is a more accurate extension of a volume measurement technique involving vector areas and centroids of cross-sections. Maximal-disc shape-based interpolation is an extension of shape-based interpolation which uses maximal disc representations to adjust the interpolation direction locally and hence improve the quality of the surface generated. Both methods are tested in simulation and in vivo. Volumes estimated using cubic planimetry are more accurate than step-section planimetry, and require fewer cross-sections, even for complex objects. Maximal-disc shape-based interpolation provides a reliable means of reconstructing surfaces from a handful of cross-sections, and can therefore be used to give confidence in the segmentation and hence also the cubic planimetry volume.

Two- and three-dimensional ultrasound in the development of a needle-free injection system.

Ultrasound was used to assess a needle-free injection device for both intradermal and subcutaneous injections. The aim of this study was, first, to differentiate intradermal from subcutaneous injections, both in vivo and in vitro using 2D ultrasound, and second, to quantify the amount of injectate that actually arrives within the dermis or subcutaneous tissues using volume measurements derived from high-resolution 3D ultrasound data sets, using a freehand system (Stradx), developed by the Cambridge University Departments of Engineering and Radiology. For the in vitro study the devices were filled with dye and injected into a pig preparation. The injection site was examined with high-resolution ultrasound and subsequently dissected to locate the injected dye with respect to the dermis. For the in vivo study, 8 volunteers received needle-free injections of normal saline. High-resolution 2D images and 3D data sets were obtained of the injected sites. Proprioceptive information for the 3D data sets was produced using an optically tracked freehand system. Segmentation of the 3D data sets gave an estimation of the volume of injected material (injectate) within the dermis. The results demonstrated that 2D ultrasound could identify the location of the injectate in the in vitro experiments and successfully distinguished an intradermal from a subcutaneous injection. In the in vivo study, 2D ultrasound clearly demonstrated the injectate location within the volunteers' dermis but was less able to demonstrate the dispersion of injectate within the subcutaneous tissues.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.

3-D ultrasonic strain imaging using freehand scanning and a mechanically-swept probe.

This paper compares 2 approaches to 3-D ultrasonic axial strain imaging: a tracked ultrasound probe swept manually over a volume, and a mechanically-swept 3-D probe. We find that high-quality data are more easily obtained using the 3-D probe, but the freehand approach may be more practical in certain scanning situations.

Initial clinical experience of an ultrasonic strain imaging system with novel noise-masking capability.

Quasistatic strain imaging is a form of elastography that can produce qualitative images of tissue stiffness with only software modifications to conventional ultrasound hardware. Unlike current commercial offerings, the novel strain-imaging system that is the subject of this paper displays regions of signal decorrelation using an overlaid colour mask and can also produce three-dimensional (3D) strain images. In illustrative studies of the breast, testis and thyroid, the colour mask is seen to reduce the potential to misinterpret noise as meaningful stiffness information, and also helps to differentiate cystic and solid lesions. High-quality imaging of the testis in vivo demonstrates that 3D strain imaging is feasible.

High resolution cortical bone thickness measurement from clinical CT data.

The distribution of cortical bone in the proximal femur is believed to be a critical component in determining fracture resistance. Current CT technology is limited in its ability to measure cortical thickness, especially in the sub-millimetre range which lies within the point spread function of today's clinical scanners. In this paper, we present a novel technique that is capable of producing unbiased thickness estimates down to 0.3mm. The technique relies on a mathematical model of the anatomy and the imaging system, which is fitted to the data at a large number of sites around the proximal femur, producing around 17,000 independent thickness estimates per specimen. In a series of experiments on 16 cadaveric femurs, estimation errors were measured as -0.01+/-0.58mm (mean+/-1std.dev.) for cortical thicknesses in the range 0.3-4mm. This compares with 0.25+/-0.69mm for simple thresholding and 0.90+/-0.92mm for a variant of the 50% relative threshold method. In the clinically relevant sub-millimetre range, thresholding increasingly fails to detect the cortex at all, whereas the new technique continues to perform well. The many cortical thickness estimates can be displayed as a colour map painted onto the femoral surface. Computation of the surfaces and colour maps is largely automatic, requiring around 15min on a modest laptop computer.

Evaluation of a three-dimensional ultrasound localisation system incorporating probe pressure correction for use in partial breast irradiation.

This work evaluates a three-dimensional (3D) freehand ultrasound-based localisation system with new probe pressure correction for use in partial breast irradiation. Accuracy and precision of absolute position measurement was measured as a function of imaging depth (ID), object depth, scanning direction and time using a water phantom containing crossed wires. To quantify the improvement in accuracy due to pressure correction, 3D scans of a breast phantom containing ball bearings were obtained with and without pressure. Ball bearing displacements were then measured with and without pressure correction. Using a single scan direction (for all imaging depths), the mean error was <1.3 mm, with the exception of the wires at 68.5 mm imaged with an ID of 85 mm, which gave a mean error of -2.3 mm. Precision was greater than 1 mm for any single scan direction. For multiple scan directions, precision was within 1.7 mm. Probe pressure corrections of between 0 mm and 2.2 mm have been observed for pressure displacements of 1.1 mm to 4.2 mm. Overall, anteroposterior position measurement accuracy increased from 2.2 mm to 1.6 mm and to 1.4 mm for the two opposing scanning directions. Precision is comparable to that reported for other commercially available ultrasound localisation systems, provided that 3D image acquisition is performed in the same scan direction. The existing temporal calibration is imperfect and a "per installation" calibration would further improve the accuracy and precision. Probe pressure correction was shown to improve the accuracy and will be useful for the localisation of the excision cavity in partial breast radiotherapy.