Axial strain imaging has been utilized for the characterization of breast masses for over a decade; however, another important feature namely the shear strain distribution around breast masses has only recently been used. In this paper, we examine the feasibility of utilizing in-vivo axial-shear strain imaging for differentiating benign from malignant breast masses. Radiofrequency data was acquired using a VFX 13-5 linear array transducer on 41 patients using a Siemens SONOLINE Antares real-time clinical scanner at the University of Wisconsin Breast Cancer Center. Free-hand palpation using deformations of up to 10% was utilized to generate axial strain and axial-shear strain images using a two-dimensional cross-correlation algorithm from the radiofrequency data loops. Axial-shear strain areas normalized to the lesion size, applied strain and lesion strain contrast was utilized as a feature for differentiating benign from malignant masses. The normalized axial-shear strain area feature estimated on 8 patients with malignant tumors and 33 patients with fibroadenomas was utilized to demonstrate its potential for lesion differentiation. Biopsy results were considered the diagnostic standard for comparison. Our results indicate that the normalized axial-shear strain area is significantly larger for malignant tumors when compared to benign masses such as fibroadenomas. Axial-shear strain pixel values greater than a specified threshold, including only those with correlation coefficient values greater than 0.75, were overlaid on the corresponding B-mode image to aid in diagnosis. A scatter plot of the normalized area feature demonstrates the feasibility of developing a linear classifier to differentiate benign from malignant masses. The area under the receiver operator characteristic curve utilizing the normalized axial-shear strain area feature was 0.996, demonstrating the potential of this feature to noninvasively differentiate between benign and malignant breast masses.

In current ultrasound elastography, only the axial component of the displacement vector is estimated and used to produce strain images. A method was recently proposed by our group to estimate both the axial and lateral components of a displacement vector following a uniaxial compression. Previous work evaluated the technique using both simulations and a mechanically translated phased array transducer. In this paper, we present initial results using beam steering on a linear array transducer attached to a commercial scanner to acquire echo signals for estimating 2-D displacement vectors. Single-inclusion and anthropomorphic breast phantoms with different boundary properties between the inclusion and background material are imaged by acquiring echo data along beam lines ranging from −15° to 15° relative to the compression direction. 1-D cross-correlation is used to calculate "angular displacements" in each acquisition direction, yielding axial and lateral components of the displacement vector. Strain tensor components are estimated from these displacements. Features on shear strain images generated for the inclusion phantom agree with those predicted using FEA analysis. Experimental results demonstrate the utility of this technique on clinical scanners. Shear strain tensors obtained using this method may provide useful information for the differentiation of benign from malignant tumors. For the linear array transducer used in this study, the optimum angular increment is around 3°. However, more work is required for the selection of an appropriate value for the maximum beam angle for optimal performance of this technique.

Spatial-angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Under this method, compounded elastograms are obtained from a spatially weighted average of local strain estimated from radio frequency (rf) echo signals acquired at different insonification angles. In previous work, the acquisition of the rf signals was performed through the lateral translation of a phased-array transducer. Clinical applications of angular compounding would, however, require the utilization of beam steering on linear-array transducers to obtain angular data sets, which is more efficient than translating phased-array transducers. In this article, we investigate the performance of angular compounding for elastography by using beam steering on a linear-array transducer. Quantitative experimental results demonstrate that spatial angular compounding provides significant improvement in both the elastographic signal-to-noise ratio and the contrast-to-noise ratio. For the linear array transducer used in this study, the optimum angular increment is around 1.5°-3.75°, and the maximum angle that can be used in angular compounding should not exceed 10°.

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Spatial-angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Previous results using spatial angular compounding, however, were based on the use of the tissue incompressibility assumption. Compounded elastograms were obtained from a spatially-weighted average of local strain estimated from radiofrequency echo signals acquired at different insonification angles. In this paper, we present a new method for reducing the noise artifacts in the axial strain elastogram utilizing a least-squares approach on the angular displacement estimates that does not use the incompressibility assumption. This method produces axial strain elastograms with higher image quality, compared to noncompounded axial strain elastograms, and is referred to as the least-squares angular-compounding approach for elastography. To distinguish between these two angular compounding methods, the spatial-angular compounding with angular weighting based on the tissue incompressibility assumption is referred to as weighted compounding. In this paper, we compare the performance of the two angular-compounding techniques for elastography using beam steering on a linear-array transducer. Quantitative experimental results demonstrate that least-squares compounding provides comparable but smaller improvements in both the elastographic signal-tonoise ratio and the contrast-to-noise ratio, as compared to the weighted-compounding method. Ultrasound simulation results suggest that the least-squares compounding method performs better and provide accurate and robust results when compared to the weighted compounding method, in the case where the incompressibility assumption does not hold.

In this article we investigate the generation of shear strain elastograms induced using a lateral shear deformation. Ultrasound simulation and experimental results demonstrate that the shear strain elastograms obtained under shear deformation exhibit significant differences between bound and unbound inclusions in phantoms, when compared to shear strain images induced upon an axial compression. A theoretical model that estimates the decorrelation between pre-and postdeformation radio frequency signals, as a function of extent of shear deformation, is also developed. Signal-tonoise ratios of shear strain elastograms obtained at different shear angles are investigated theoretically and verified using ultrasound simulations on a uniformly elastic phantom. For the simulation and experiment, a two-dimensinal block-matching-based algorithm is used to estimate the axial and lateral displacement. Shear strains are obtained from the displacement vectors using a least-squares strain estimator. Our results indicate that the signal-to-noise ratio (SNR) of shear strain images increases to reach a maximum and saturates, and then decreases with increasing shear angle. Using typical system parameters, the maximum achievable SNR for shear strain elastography is around 8 (18 dB), which is comparable to conventional axial strain elastography induced by axial compression. Shear strain elastograms obtained experimentally using single inclusion tissue-mimicking phantoms with both bound and unbound inclusions (mimicking cancerous masses and benign fibroadenomas, respectively) demonstrate the characteristic differences in the depiction of these inclusions on the shear strain elastograms.

Signal decorrelation is a major source of error in the displacements estimated using correlation techniques for elastographic imaging. Previous papers have addressed the variation in the correlation coefficient as a function of the applied compression for a finite window size and an insonification angle of zero degrees. The recent use of angular beam-steered radio-frequency echo signals for spatial angular compounding and shear strain estimation have demonstrated the need for understanding signal decorrelation artifacts for data acquired at different beam angles. In this paper, we provide both numerical and closed form theoretical solutions of the correlation between pre-and postcompression radio-frequency echo signals acquired at a specified beam angle. The expression for the correlation coefficient obtained is a function of the beam angle and the applied compression for a finite duration window. Accuracy of the theoretical results is verified using tissue-mimicking phantom experiments on a uniformly elastic phantom using beam-steered data acquisitions on a linear array transducer. The theory predicts a faster decorrelation with changes in the beam or insonification angle for longer radio-frequency echo signal segments and at deeper locations in the medium. Theoretical results provide useful information for improving angular compounding and shear strain estimation techniques for elastography.

Actinomycetes have evolved in the process of ecological interactions between animals, plants and microorganisms in the environment to produce new classes of secondary metabolites with novel structures, 1-3 of which polyene macrolides are very interesting bioactive compounds with a wide range of biological activities and subject to a relatively low incidence of resistance. 4,5 Many of these molecules have been successfully isolated and turned into useful drugs and other organic chemicals. In our study aimed at the discovering of novel antifungals, the soil actinomycete, Streptomyces lavenduligriseus, was found to produce strong antifungal components. Bioactivity-guided isolation and purification yielded filipin III 1 and three novel polyene macrolides, compound 2, 3 and 4 ( Figure 1). Details of the isolation, structure elucidation and the antifungal activities of these compounds are presented below.The strain of S. lavenduligriseus was cultivated in 250-ml Erlenmeyer flasks containing 30 ml of seed medium (2% glucose, 3% soybean meal, 2% soluble starch, 2% glycerol, 0.02% MgSO 4 ·7H 2 O and 0.02% KH 2 PO 4 , pH 7.5). The flasks were shaken at 220 r.p.m. on a rotary shaker at 28°C for 2 days. The seed culture (8%) was transferred into 500-ml Erlenmeyer flasks containing 50 ml of production medium (4% cornstarch, 0.8% glucose, 2.2% soybean meal, 0.1% MgSO 4 ·7H 2 O, 0.02% KH 2 PO 4 and 0.2% NaCl). The flasks were incubated at 220 r.p.m. on a rotary shaker at 28°C for 7 days. The cells were lysed with EtOH, which was then removed by concentration in vacuo. The resulting aqueous concentrate was partitioned successively with EtOAc (3 × 3 l) and BuOH (3 × 3 l). The combined extracts were concentrated under reduced pressure to yield 68 g of brown gum. This material was subjected to silica gel chromatography using a gradient mixture of CHCl 3 -MeOH (from 100:0 to 0:100), yielding nine fractions (A-I). A fraction (5.65 g) was identified as containing polyene macrolides by assaying for bioactivity against Candida albicans and by a diode array detector (DAD)/UV spectra with three characteristic λ max at 289, 303, 319 nm. 6 The fraction was further fractionated by successive preparative HPLC (YMC-Pack RP-C18 (YMC, Tokyo, Japan), 30 × 250 mm 2 , 35% MeCN in H 2 O, 10 mlmin − 1 ), yielding fractions 1-8. Fraction 3 (26.5 mg) was further purified by semi-prep RP-HPLC (YMC-Pack RP-C18, 20 × 250 mm 2 , 35% MeCN in H 2 O, 7 ml min − 1 ) to attain compound 4 (23.6 mg; t R = 20.1 min). Using the same procedure, purification of fraction 6 (56.5 mg) yielded compounds 3 (8.3 mg; t R = 72.6 min) and 2 (7.3 mg; t R = 81.2 min), fraction 8 (69.5 mg) afforded compound 1 (12.6 mg; t R = 63.5 min).Compound 1 was identified as filipin III by comparing its NMR and MS data with those previously reported. 7 The molecular formula of compound 2 was determined to be C 38 H 64 O 13 (seven degrees of unsaturation) on the basis of its positive HR-ESI-MS at the m/z value = 751.4226 [M+Na] + , 74 a.m.u. higher than that of compound 1, in agreement with ...