Multiparametric ultrasound examination for response assessment in breast cancer patients undergoing neoadjuvant therapy.

To investigate the performance of multiparametric ultrasound for the evaluation of treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Breast cancer patients who were scheduled to undergo NAC were invited to participate in this study. Changes in tumour echogenicity, stiffness, maximum diameter, vascularity and integrated backscatter coefficient (IBC) were assessed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was considered as standard of reference. RMC < 30% was considered a good response and > 70% a poor response. The correlation coefficients of these parameters were compared with RMC from post-operative histology. Linear Discriminant Analysis (LDA), cross-validation and Receiver Operating Characteristic curve (ROC) analysis were performed. Thirty patients (mean age 56.4 year) with 42 lesions were included. There was a significant correlation between RMC and echogenicity and tumour diameter after the 3rd course of NAC and average stiffness after the 2nd course. The correlation coefficient for IBC and echogenicity calculated after the first four doses of NAC were 0.27, 0.35, 0.41 and 0.30, respectively. Multivariate analysis of the echogenicity and stiffness after the third NAC revealed a sensitivity of 82%, specificity of 90%, PPV = 75%, NPV = 93%, accuracy = 88% and AUC of 0.88 for non-responding tumours (RMC > 70%). High tumour stiffness and persistent hypoechogenicity after the third NAC course allowed to accurately predict a group of non-responding tumours. A correlation between echogenicity and IBC was demonstrated as well.

High frequency ultrasonography: a complementary diagnostic method in evaluation of primary cutaneous melanoma.

AIM: The aim of our study was to assess the usefulness of high frequency ultrasonography in the diagnosis of melanoma. METHODS: We examined 84 patients with suspicious melanocytic skin lesions, including 19 cases of melanoma. In vivo high-resolution ultrasonography (30 MHz) was performed prior to excision. RESULTS: In ultrasound scans early melanomas presented as flat oval or fusiform shaped structures and were clearly demarcated, while advanced melanomas were characterized by a roundish shape with less distinct borders. The ultrasonographic thickness of in situ melanomas ranged from 0.02 to 0.85 mm. In the case of invasive tumors, the mean thickness evaluated by high frequency ultrasonography was 10.7% higher compared to the Breslow Score (1.44±0.8 mm and 1.3±0.88 mm, respectively). In all melanomas of Breslow Score of 1 mm or more ultrasound also indicated a Breslow Score of 1 mm or more. CONCLUSION: High frequency ultrasound examination has limited value in differential diagnosis of melanoma, but it gives a clear picture of the size and depth of the tumor. The method should be used as a complementary method (after dermoscopy and, where applicable, reflectance confocal microscopy) in preoperative evaluation of the tumor. In some cases of locally advanced melanoma, ultrasound examination may allow to reduce the number of surgical procedures and favor the decision of a one-time surgical treatment (removal of primary tumor and sentinel lymph node biopsy at the same time).

Modeling and analysis of multiple scattering of acoustic waves in complex media: application to the trabecular bone.

The integral equations that describe scattering in the media with step-rise changing parameters have been numerically solved for the trabecular bone model. The model consists of several hundred discrete randomly distributed elements. The spectral distribution of scattering coefficients in subsequent orders of scattering has been presented. Calculations were carried on for the ultrasonic frequency ranging from 0.5 to 3 MHz. Evaluation of the contribution of the first, second, and higher scattering orders to total scattering of the ultrasounds in trabecular bone was done. Contrary to the approaches that use the µCT images of trabecular structure to modeling of the ultrasonic wave propagation condition, the 3D numerical model consisting of cylindrical elements mimicking the spatial matrix of trabeculae, was applied. The scattering, due to interconnections between thick trabeculae, usually neglected in trabecular bone models, has been included in calculations when the structure backscatter was evaluated. Influence of the absorption in subsequent orders of scattering is also addressed. Results show that up to 1.5 MHz, the influence of higher scattering orders on the total scattered field characteristic can be neglected while for the higher frequencies, the relatively high amplitude interference peaks in higher scattering orders clearly occur.

Comparison of sound fields generated by different coded excitations--experimental results.

This work reports the results of measurements of spatial distributions of ultrasound fields obtained from five energizing schemes. Three different codes, namely, chirp signal and two sinusoidal sequences were investigated. The sequences were phase modulated with 13 bits Barker code and 16 bits Golay complementary codes. Moreover, two reference signals generated as two and sixteen cycle sine tone bursts were examined. Planar, 50% (fractional) bandwidth, 15 mm diameter source transducer operating at 2 MHz center frequency was used in all measurements. The experimental data were collected using computerized scanning system and recorded using wideband, PVDF membrane hydrophone (Sonora 804). The measured echoes were compressed, so the complete pressure field in the investigated location before and after compression could be compared. In addition to a priori anticipated increase in the signal to noise ratio (SNR) for the decoded pressure fields, the results indicated differences in the pressure amplitude levels, directivity patterns, and the axial distance at which the maximum pressure amplitude was recorded. It was found that the directivity patterns of non-compressed fields exhibited shapes similar to the patterns characteristic for sinusoidal excitation having relatively long time duration. In contrast, the patterns corresponding to compressed fields resembled those produced by brief, wideband pulses. This was particularly visible in the case of binary sequences. The location of the maximum pressure amplitude measured in the 2 MHz field shifted towards the source by 15 mm and 25 mm for Barker code and Golay code, respectively. The results of this work may be applicable in the development of new coded excitation schemes. They could also be helpful in optimizing the design of imaging transducers employed in ultrasound systems designed for coded excitation. Finally, they could shed additional light on the relationship between the spatial field distribution and achievable image quality and in this way facilitate optimization of the images obtained using coded systems.

Estimation of ultrasonic attenuation in a bone using coded excitation.

This paper describes a novel approach to estimate broadband ultrasound attenuation (BUA) in a bone structure in human in vivo using coded excitation. BUA is an accepted indicator for assessment of osteoporosis. In the tested approach a coded acoustic signal is emitted and then the received echoes are compressed into brief, high amplitude pulses making use of matched filters and correlation receivers. In this way the acoustic peak pressure amplitude probing the tissue can be markedly decreased whereas the average transmitted intensity increases proportionally to the length of the code. This paper examines the properties of three different transmission schemes, based on Barker code, chirp and Golay code. The system designed is capable of generating 16 bits complementary Golay code (CGC), linear frequency modulated (LFM) chirp and 13-bit Barker code (BC) at 0.5 and 1 MHz center frequencies. Both in vivo data acquired from healthy heel bones and in vitro data obtained from human calcaneus were examined and the comparison between the results using coded excitation and two cycles sine burst is presented. It is shown that CGC system allows the effective range of frequencies employed in the measurement of broadband acoustic energy attenuation in the trabecular bone to be doubled in comparison to the standard 0.5 MHz pulse transmission. The algorithm used to calculate the pairs of Golay sequences of the different length, which provide the temporal side-lobe cancellation is also presented. Current efforts are focused on adapting the system developed for operation in pulse-echo mode; this would allow examination and diagnosis of bones with limited access such as hip bone.

Skin imaging with high frequency ultrasound - preliminary results.

This study presents the detailed construction and the principle of performance of high frequency (HF) ultrasound scanner for skin examination. The aim of this study was to show a difference between diseased and healthy skin and to evaluate the usefulness of the scanner in monitoring of therapeutic efficacy of morphea and lichen sclerosus et atrophicus (LSA). We examined 48 patients aged between 15 and 64 years; 25 patients with plaque-type morphea, nine patients with linear morphea and 14 patients with LSA. In the course of 18 months all patients were examined before, during and after treatment. In 29 patients ultrasonographic evidence of regression (decreasing of the skin thickness) was observed, in eight patients ultrasound examination showed progression and in 12 patients no difference in the ultrasound scan before and after treatment could be shown. Our study shows that HF ultrasound scanner is suitable to differentiate between the healthy and diseased skin in morphea and LSA as well as to evaluate the treatment efficacy of these diseases.

Detection of bone disease with ultrasound--comparison with bone densitometry.

A system for ultrasonic in-vivo examination of a heel bone (calcaneus) was developed. When operating in transmission mode, the system can measure broadband ultrasonic attenuation-BUA, speed of sound--SOS and thickness of bone. BUA and SOS are measured by comparing the pulses transmitted through the heel with the reference pulse transmitted through water. In our approach, we operate in the backscattered mode in addition to transmission. The backscattered ultrasonic technique for bone characterization is very promising because the magnitude of backscattered waves depends on the scattering cross-section of a trabecular structure that, to some extent, describes the microarchitecture of a calcaneus. Additionally, when the backscattered and transmitted signals are compared, some of the signal distortions caused by tissue and bone interfaces are reduced. A set of data representing signals transmitted through the heel and reflected inside a calcaneus for patients with osteoporosis was collected. Several signal-processing techniques were applied in order to smooth the backscattered signal and to calculate a trabecular structure cros-section (TSC) function. Results obtained by these approaches along with a spectral shift method and a standard BUA measurement are presented and compared to X-ray bone mineral density determination results.

Acoustic microscopy of cultured cells. Distribution of forces and cytoskeletal elements.

The scanning acoustic microscope (SAM) allows one to measure mechanical parameters of living cells with high lateral resolution. By analyzing single acoustic images' sound attenuation and sound velocity, the latter corresponding to stiffness (elasticity) of the cortical cytoplasm can be determined. In this study, measurements of stiffness distribution in XTH-2 cells were compared with the organization of F-actin and microtubules. Single XTH-2 cells exhibit relatively high stiffness at the free margins; toward the cell center this value decreases and reaches a sudden minimum where the slope of the surface topography enlargens at the margin of the dome-shaped cell center. The steepness of the increase in slope is linearly related to the decrease in sound velocity at this site. Thus, a significant determinant of cell shape is paralleled by an alteration of stiffness. In the most central parts, no interferences could be distinguished, therefore, this region had to be excluded from the calculations. Stiffness distribution roughly coincided with the distribution of F-actin, but no correlation to microtubule arrangement was found. Following the treatment of XTH-2 cells with ionomycin in the presence of calcium (in the culture medium), the cell cortex first contracted as indicated by shape changes and by a marked increase in stiffness (deduced from sound velocity). This contraction phase was followed by a phase of microtubule and F-actin disassembly. Concomittantly, sound velocity decreased considerably, indicating the loss of elasticity in the cell cortex. No structural equivalent to sound attenuation has been identified.

Measurements of cells in culture by scanning acoustic microscopy.

A novel method allowing the determination of thickness, attenuation and impedance of both living and fixed cells in culture using a single image recorded with a scanning acoustic microscope is described. The method is based on the recording of the image data locating the surface of the cell far below the geometric focus. In this way only the normal incident acoustic wave is used for image formation. Higher values of impedance and attenuation coefficients were found in the cell periphery than in the central part of the cell. This phenomenon is suggested to be due to the different organization of cytoskeletal elements.

On the possibility of the visualization of the velocity distribution in biological samples using SAM.

The effect of velocity changes in a biological sample on its image, obtained by using a reflection acoustic microscope, is discussed in the case of a distance between the sample and the lens smaller than the focal length. The effect of the shift of the V(z) curve, caused by a velocity change in the material of the sample, is assumed as the main source of changes in brightness in such images. The value of the shift of V(z) curve is determined theoretically and verified experimentally for layers of glycerol and aqueous glycerol solution. The possibility of interpreting acoustic images as the images of the velocity distribution in the sample is also discussed.