Nigel L. Bush

A freehand elastographic imaging approach for clinical breast imaging: system development and performance evaluation

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.

Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema.

Abstract:  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. 

Freehand Elasticity Imaging Using Speckle Decorrelation Rate

Malignant tumours are often relatively stiff and immobile. These properties permit tumours such as breast cancers to be detected by palpation and have provided motivation for the development of new methods for imaging tissue elasticity, by ultrasonically estimating the displacement or strain distribution due to an externally applied stress. Various authors have now shown that such elasticity images may possess excellent spatial and contrast resolution1,2,3.

Spatial and acoustic pressure dependence of microbubble-mediated gene delivery targeted using focused ultrasound

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.

Targeted retroviral gene delivery using ultrasound.

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

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

Vessel orientation-dependent sensitivity of optoacoustic imaging using a linear array transducer

Abstract. 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.

Elastographic imaging of thermally ablated tissue in vitro

Focused ultrasound surgery (FUS) is a promising therapeutic technique but progress is currently limited by the need for improved imaging methods to monitor the extent of tissue damage during and immediately after FUS exposure. Thermally ablated tissue are generally stiffer relative to surrounding undamaged tissues, which suggests that it should be possible to monitor FUS using any imaging technique, such as elastography, which is capable of visualising tissue elasticity. The aim of this paper is to report the results of a preliminary investigation conducted using ex-vivo bovine liver tissues, to explore the feasibility of monitoring FUS using ultrasonic elastographic imaging. The results demonstrated that spatial and contrast resolution of elastography should be sufficiently high for monitoring focused ultrasound surgery.

High-resolution ultrasound reflex transmission imaging and digital photography: potential tools for the quantitative assessment of pigmented lesions.

Background/aims: 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.

Acoustic Cluster Therapy (ACT) — pre-clinical proof of principle for local drug delivery and enhanced uptake

Proof of principle for local drug delivery with Acoustic Cluster Therapy (ACT) was demonstrated in a human prostate adenocarcinoma growing in athymic mice, using near infrared (NIR) dyes as model molecules. A dispersion of negatively charged microbubble/positively charged microdroplet clusters are injected i.v., activated within the target pathology by diagnostic ultrasound (US), undergo an ensuing liquid-to-gas phase shift and transiently deposit 20-30μm large bubbles in the microvasculature, occluding blood flow for ~5-10min. Further application of low frequency US induces biomechanical effects that increase the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g., released or co-administered drugs). Results demonstrated deposition of activated bubbles in tumor vasculature. Following ACT treatment, a significant and tumor specific increase in the uptake of a co-administered macromolecular NIR dye was shown. In addition, ACT compound loaded with a lipophilic NIR dye to the microdroplet component was shown to facilitate local release and tumor specific uptake. Whereas the mechanisms behind the observed increased and tumor specific uptake are not fully elucidated, it is demonstrated that the ACT concept can be applied as a versatile technique for targeted drug delivery.