Amplitude based segmentation of ultrasound echoes for attenuation coefficient estimation.

In vivo ultrasound attenuation coefficient measurements are of interest as they can provide insight into tissue pathology. They are also needed so that measurements of the tissue's frequency dependent ultrasound backscattering coefficient may be corrected for attenuation. In vivo measurements of the attenuation coefficient are challenging because it has to be estimated from the depth dependent decay of backscatter signals that display a large degree of magnitude variation. In this study we describe and evaluate an improved backscatter method to estimate ultrasound attenuation which is tolerant to the presence of some backscatter inhomogeneity. This employs an automated algorithm to segment and remove atypically strong echoes to lessen the potential bias these may introduce on the attenuation coefficient estimates. The benefit of the algorithm was evaluated by measuring the frequency dependent attenuation coefficient of a gelatine phantom containing randomly distributed cellulose scatterers as a homogeneous backscattering component and planar pieces of cooked leek to provide backscattering inhomogeneities. In the phantom the segmentation algorithm was found to improve the accuracy and precision of attenuation coefficient estimates by up to 80% and 90%, respectively. The effect of the algorithm was then measured invivo using 32 radiofrequency B-mode datasets from the breasts of two healthy female volunteers, producing a 5 to 25% reduction in mean attenuation coefficient estimates and a 30 to 50% reduction in standard deviation of attenuation coefficient across different positions within each breast. The results suggest that the segmentation algorithm may improve the accuracy and precision of attenuation coefficient estimates invivo.

Rapid scanning wide-field clutter elimination in epi-optoacoustic imaging using comb LOVIT.

Epi-style optoacoustic (OA) imaging provides flexibility by integrating the irradiation optics and ultrasound receiver, yet clutter generated by optical absorption near the probe obscures deep OA sources. Localised vibration tagging (LOVIT) retrieves OA signal from images that are acquired with and without a preceding ultrasonic pushing beam: Radiation force leads to a phase shift of signals coming from the focal area resulting in their visibility in a difference image, whereas clutter from outside the pushing beam is eliminated. Disadvantages of a single-focus approach are residual clutter from inside the pushing beam above the focus, and time-intensive scanning of the focus to retrieve a large field-of-view. To speed up acquisition, we propose to create multiple foci in parallel, forming comb-shaped ARF patterns. By subtracting OA images obtained with interleaved combs, this technique moreover results in greatly improved clutter reduction in phantoms mimicking optical, acoustic and elastic properties of breast tissue.

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.

Elastographic contrast generation in optical coherence tomography from a localized shear stress.

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.

Quantitative discrimination of pigmented lesions using three-dimensional high-resolution ultrasound reflex transmission imaging.

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.

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

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.