[Breast cancer in young women in the south of Tunisia]. / Le cancer du sein de la femme jeune dans le sud tunisien.

OBJECTIVE: The objective of this retrospective study was to discuss the epidemioclinical criteria, the therapeutic results and the prognostic factors of breast cancer in young women throughout a comparative study of 72 young patients aged less than 35 years and a second group of older premenopausal patients aged between 36 and 50 years. PATIENTS AND METHODS: We reviewed the epidemioclinical records of all the patients. Non-metastatic and operable patients were treated with surgery (conservative or radical) followed by an adjuvant treatment (chemotherapy, radiotherapy, endocrine therapy) indicated according to the prognostic factors. Locally advanced or metastatic tumors were treated with chemotherapy. Overall survival was calculated according to the Kaplan-Meier method. The comparison of survival curves was performed according to log-rank test. The multivariate analysis was performed according to the Cox model. RESULTS: The mean age was of 31.5 years. T2N1, node positive (N+), high grade (SBRII and III) and endocrine non-responsive tumors were the most frequent. There was no difference with the second group of older patients regarding the risk factors and the clinical criteria but mammography was more sensitive in the second group. The 5 years overall survival of young patients was of 57% and pejorative prognostic factors in univariate analysis were: tumor size, N+ and endocrine non-responsiveness. There were not any significant prognostic factors at the multivariate analysis. Young age less than 35 years was not a prognostic factor influencing overall survival in the totality of patients or in the different sub-groups according to the other prognostic factors. CONCLUSION: Clinical presentation and outcome of breast cancer in our young patients aged under 35 years seems not to be different from that in older patients. The conclusions of the different authors are controversial but the majority has reported more advanced tumors with worse prognostic than those of older patients.

Tissue-mimicking oil-in-gelatin dispersions for use in heterogeneous elastography phantoms.

A ten-month study is presented of materials for use in heterogeneous elastography phantoms. The materials consist of gelatin with or without a suspension of microscopic safflower oil droplets. The highest volume percent of oil in the materials is 50%. Thimerosal acts as a preservative. The greater the safflower oil concentration, the lower the Young's modulus. Elastographic data for heterogeneous phantoms, in which the only variable is safflower oil concentration, demonstrate stability of inclusion geometry and elastic strain contrast. Young's modulus ratios (elastic contrasts) producible in a heterogeneous phantom are as high as 2.7. The phantoms are particularly useful for ultrasound elastography. They can also be employed in MR elastography, although the highest achievable ratio of longitudinal to transverse relaxation times is considerably less than is the case for soft tissues.

The effects of digitization on the elastographic signal-to-noise ratio.

In elastography, the tissue under investigation is compressed and the resulting strain is estimated from the gradient of the displacement (time-delay) estimates. The displacements are typically estimated by cross-correlating the radiofrequency (RF) ultrasound signals of the pre- and postcompressed tissue. One of the parameters used to quantify the resulting quality of the elastogram is the elastographic signal-to-noise ratio (SNR(e)). For a uniformly elastic target (a single elastic modulus), the dependence of the SNR(e) on the applied strain has a bandpass characteristic that has been termed the strain filter. Theoretical expressions for the upper bound on the strain filter were developed earlier. Yet, simulated as well as experimental strain filters derived from uniformly elastic phantoms deviate from these upper bounds. The failure to achieve the upper bounds could be partially attributed to the fact that, in both simulations and experiments, the RF signals used to compute the TDEs are sampled and quantized. Using simulated models of uniformly elastic phantoms, a study of the dependence of the strain filter on the quantization and sampling rates was performed. The results indicated that the strain filter improves with both the sampling rate and the quantization, as expected. A theoretical analysis was done to incorporate quantization as a derating factor to the strain filter.

Analysis of an adaptive strain estimation technique in elastography.

Elastography is based on the estimation of strain due to tissue compression or expansion. Conventional elastography involves computing strain as the gradient of the displacement (time-delay) estimates between gated pre- and postcompression signals. Uniform temporal stretching of the postcompression signals has been used to reduce the echo-signal decorrelation noise. However, a uniform stretch of the entire postcompression signal is not optimal in the presence of strain contrast in the tissue and could result in loss of contrast in the elastogram. This has prompted the use of local adaptive stretching techniques. Several adaptive strain estimation techniques using wavelets, local stretching and iterative strain estimation have been proposed. Yet, a quantitative analysis of the improvement in quality of the strain estimates overconventional strain estimation techniques has not been reported. We propose a two-stage adaptive strain estimation technique and perform a quantitative comparison with the conventional strain estimation techniques in elastography. In this technique, initial displacement and strain estimates using global stretching are computed, filtered and then used to locally shift and stretch the postcompression signal. This is followed by a correlation of the shifted and stretched postcompression signal with the precompression signal to estimate the local displacements and hence the local strains. As proof of principle, this adaptive stretching technique was tested using simulated and experimental data.

Estimating the elastographic signal-to-noise ratio using correlation coefficients.

In conventional elastography, strain is estimated from the gradient of the displacement (time-delay) estimates. The displacement estimates involve estimating the peak location of the cross-correlation function between matching pre- and post-compression A-lines. Bias errors in estimating the peak location of the cross-correlation function, amplified by the gradient operation on the displacement estimates (needed for the computation of the strain), could result in values of elastographic signal-to-noise ratio (SNR(e)) that exceed the theoretical upper bounds, thereby hindering a consistent interpretation of this parameter. These algorithmic errors have not been accounted for by the theory. We propose the use of the measured correlation coefficients in the theoretical SNR(e) expressions to estimate the SNR(e), rather than computing them directly from the elastograms. This methodology results in values of SNR(e) that are lower than the theoretical upper bounds, thereby avoiding the problems associated with computing SNR(e) directly from the elastograms. Using simulated models of uniformly elastic phantoms, a proof of principle of such an SNR(e) measure is shown.

Contrast-transfer efficiency for continuously varying tissue moduli: simulation and phantom validation.

This study consisted of two parts. In the first part, the contrast-transfer efficiency (CTE) in elastography was extended to account for continuous changes of modulus distribution. It was shown that, for a finite size background, the strain contrast approaches the modulus contrast in the case of Gaussian distributions. Thus, an increase in the CTE was obtained. For a fixed background size, it was shown that the CTE increases as the SD of the Gaussian distribution increases. This property was explained by the redistribution of strain concentrations at the inclusion/background interface. In the second part of the study, the CTE was verified experimentally. Six gelatin/agar/water-based phantoms embedding inclusions with modulus contrast varying between +/- 6 dB were manufactured. It was shown that the modulus at the interface inclusion/background was continuous and, in turn, resulted in an increase of the CTE as compared to the known case of a sharp boundary. The continuous inclusion/background interface was explained by the existence of an osmotic pressure gradient.

Tradeoffs in elastographic imaging.

This paper presents the tradeoffs in elastographic imaging. Elastography is viewed as a new imaging modality and presented in terms of three fundamental concepts that constitute the basis for the elastographic imaging process. These are the tissue elastic deformation process, the statistical analysis of strain estimation and the image characterization. The first concept involves the use of the contrast transfer efficiency (CTE) that describes the mapping of a distribution of local tissue elastic moduli into a distribution of local longitudinal tissue strains. The second concept defines the elastographic system and the relationship between ultrasonic and signal processing parameters. This process is described in terms of a stochastic framework (the strain filter) that provides upper and practical performance bounds and their dependence on the various system parameters. Finally, the output image, the elastogram, is characterized by its image parameters, such as signal-to-noise ratio, contrast-to-noise ratio, dynamic range and resolution. Finite-element simulations are used to generate examples of elastograms that are confirmed by the theoretical prediction tools.

Elastographic imaging of the normal canine prostate in vitro.

Elastography has been shown to be successful in mapping the relative mechanical attributes of normal as well as abnormal tissues. In this study, the histological characteristics of freshly excised normal canine prostates were used to explain consistently depicted elastographic features. The elastograms of the transverse cross-sections across the urethra demonstrated a consistent symmetry of the gland as well as clear anatomic structures. These include a central portion of the gland surrounding the urethra and a peripheral gland. The central gland was consistently softer than the peripheral gland. At the level of the verumontanum, depicted as a small stiff ridge, the lumen of the urethra was consistently demonstrated as an inverted soft 'u' or 'v' shaped area. The network of branching-fibrous connective tissue septa was depicted by the elastogram as linear features, which converged on the urethra. In the anterior side of the gland, the fibromuscular stroma was seen as a circumscribed hard tissue. In the sagittal view, the elastogram suggested a stiff peripheral zone surrounding a softer central zone, which is traversed by the urethra depicted as soft tissue.

Elastographic characterization of HIFU-induced lesions in canine livers.

The elastographic visualization and evaluation of high-intensity focused ultrasound (HIFU)-induced lesions were investigated. The lesions were induced in vitro in freshly excised canine livers. The use of different treatment intensity levels and exposure times resulted in lesions of different sizes. Each lesion was clearly depicted by the corresponding elastogram as being an area harder than the background. The strain contrast of the lesion/background was found to be dependent on the level of energy deposition. A lesion/background strain contrast between -2.5 dB and -3.5 dB was found to completely define the entire zone of tissue damage. The area of tissue damage was automatically estimated from the elastograms by evaluating the number of pixels enclosed inside the isointensity contour lines corresponding to a strain contrast of -2.5, -3 and -3.5 dB. The area of the lesion was measured from a tissue photograph obtained at approximately the same plane where elastographic data were collected. The estimated lesion areas ranged between approximately 10 mm2 and 110 mm2. A high correlation between the damaged areas as depicted by the elastograms and the corresponding areas as measured from the gross pathology photographs was found (r2 = 0.93, p value < 0.0004, n = 16). This statistically significant high correlation demonstrates that elastography has the potential to become a reliable and accurate modality for HIFU therapy monitoring.

Elastography: ultrasonic estimation and imaging of the elastic properties of tissues.

The basic principles of using sonographic techniques for imaging the elastic properties of tissues are described, with particular emphasis on elastography. After some preliminaries that describe some basic tissue stiffness measurements and some contrast transfer limitations of strain images are presented, four types of elastograms are described, which include axial strain, lateral strain, modulus and Poisson's ratio elastograms. The strain filter formalism and its utility in understanding the noise performance of the elastographic process is then given, as well as its use for various image improvements. After discussing some main classes of elastographic artefacts, the paper concludes with recent results of tissue elastography in vitro and in vivo.

The feasibility of elastographic visualization of HIFU-induced thermal lesions in soft tissues. Image-guided high-intensity focused ultrasound.

The potential for visualizing high-intensity focused ultrasound (HIFU)-induced thermal lesions in biological soft tissues in vitro using elastography was investigated. Thermal lesions were created in rabbit paraspinal skeletal muscle in vivo. The rabbits were sacrificed 60 h following the treatment and lesioned tissues were excised. The tissues were cast in a block of clear gel and elastographic images of the lesions were acquired. Gross pathology of the tissue samples confirmed the characteristics of the lesions.

The use of elastography to measure quality characteristics of pork semimembranosus muscle.

The objectives of this study were to determine if ultrasonic strain image analysis could estimate pork eating quality parameters (such as fresh color, drip loss, and Warner/Bratzler shear). Intact semimembranosus (SM) muscles (cap off) were analyzed for ultimate pH (pH(ult)). Forty-five SM muscles were selected from the larger allotment of fresh hams over a 3-week period. The SM muscles were selected based on high and low pH(ult) in an attempt to represent a wide range of pork quality. Ultrasonic strain images were obtained perpendicular to the SM muscle fibers of an 8-cm cube. Radio-frequency data from each SM were obtained from a field-of-view (FOV) of 40×30 mm(2) and digitized for each compression step. Tissue displacements were computed for each compression step. Tissue strains were computed from displacement data located in the FOV representing areas of harder and softer muscle tissue and converted to gray scale images at 256 levels. Tissue irregularity of hardness and softness was measured using Fractal dimension and Haralicks parameters. Twenty-one Fractal dimension (FR) parameters, at two neighborhood distances (N), from each strain image and nine Haralick's (HAR) textural parameters (inter-pixel distance=1) were analyzed for each image. The variable FR4N4 had a -0.279 correlation with SM ultimate pH (p<0.10); FR6N8 correlated to WB shear force at 0.325 (p<0.05); and FR21N8 had a correlation coefficient of 0.364 with intramuscular fat (p<0.01). Linear regression equations generated from FRN and HAR parameters for intramuscular fat (R(2)=0.468), Warner/Bratzler shear (R(2)=0.360), and 30 h drip loss (R(2)=0.208). Although elastographic measurement was significantly correlated to shear (p<0.05), a better understanding of physical meat texture is necessary before elastography can be used to identify superior quality pork.

Limits on the contrast of strain concentrations in elastography.

Using an analytic solution of the elasticity equation derived for a cylindrical inclusion, it is shown that the contrast of the strain concentrations is limited for both hard and soft lesions. This means that, beyond a given elastic modulus contrast, the strain concentrations remain virtually constant.

Elastographic imaging of low-contrast elastic modulus distributions in tissue.

Elastography is a new ultrasonic imaging technique that produces images of the strain distribution in compliant tissues. This strain distribution is derived from ultrasonically estimated longitudinal internal motion induced by an external compression of the tissue. The displayed two-dimensional (2-D) images are called elastograms. In this paper, it is demonstrated that, when signal-to-noise ratio-enhancing techniques are used, elastography is capable of imaging low-contrast elastic modulus tissue structures with high contrast-to-noise ratios. This is demonstrated using both computer simulations and data obtained from 3 days postmortem ovine kidneys in vitro. The elastograms of such organs suggest that the modulus slowly decays from the renal cortex (RC) to the interior of the renal sinus (RS). Such modulus variation is corroborated by independent measurements of the Young's moduli. It is found that the RC is approximately twice as hard as the interior of the RS. We invoke our previous results on elastographic contrast-transfer efficiency to demonstrate that, at low contrast, the elastogram may be interpreted as a quantitative image of the relative Young's modulus distribution.

Elastic moduli of breast and prostate tissues under compression.

To evaluate the dynamic range of tissue imaged by elastography, the mechanical behavior of breast and prostate tissue samples subject to compression loading has been investigated. A model for the loading was validated and used to guide the experimental design for data collection. The model allowed the use of small samples that could be considered homogeneous; this assumption was confirmed by histological analysis. The samples were tested at three strain rates to evaluate the viscoelastic nature of the material and determine the validity of modeling the tissue as an elastic material for the strain rates of interest. For loading frequencies above 1 Hz, the storage modulus accounted for over 93 percent of the complex modulus. The data show that breast fat tissue has a constant modulus over the strain range tested while the other tissues have a modulus that is dependent on the strain level. The fibrous tissue samples from the breast were found to be 1 to 2 orders of magnitude stiffer than fat tissue. Normal glandular breast tissue was found to have an elastic modulus similar to that of fat at low strain levels, but the modulus of the glandular tissue increased by an order of magnitude above fat at high strain levels. Carcinomas from the breast were stiffer than the other tissues at the higher strain level; intraductal in situ carcinomas were like fat at the low strain level and much stiffer than glandular tissue at the high strain level. Infiltrating ductal carcinomas were much stiffer than any of the other breast tissues. Normal prostate tissue has a modulus that is lower than the modulus of the prostate cancers tested. Tissue from prostate with benign prostatic hyperplasia (BPH) had modulus values significantly lower than normal tissue. There was a constant but not significant difference in the modulus of tissues taken from the anterior and posterior portions of the gland.

Elastographic imaging of thermal lesions in soft tissue: a preliminary study in vitro.

The use of elastography for the visualization of thermal lesions in biological soft tissue in vitro was investigated. Thermal lesions were created in samples of postmortem ovine kidney using a surgical neodymium: YAG (Nd:YAG) laser. The kidney samples were cast in gel, and elastographic images of the lesions were constructed using sonographic information and external markers to locate the region of interest. Gross pathology of the kidney samples confirmed the dimensions of the lesions. Good correlation between the lesion length along the laser fiber axis and maximum diameter measured off of the fiber axis determined from elastographic images and gross pathology photographs was found.

A least-squares strain estimator for elastography.

A least-squares strain estimator (LSQSE) for elastography is proposed. It is shown that with such an estimator, the signal-to-noise ratio in an elastogram (SNRe) is significantly improved. This improvement is illustrated theoretically using a modified strain filter and experimentally using a homogeneous gel phantom. It is demonstrated that the LSQSE results in an increase of the elastographic sensitivity (smallest, strain that could be detected), thereby increasing the strain dynamic range. Using simulated data, it is shown that a tradeoff exists between the improvement in SNRe and the reduction of strain contrast and spatial resolution.

Elastographic dynamic range expansion using variable applied strains.

In elastography, we want to image the entire range of stiffnesses of the elastic components found in inhomogeneous tissues. In order to achieve this, the elastographic dynamic range should equal the entire stiffness dynamic range in the target. Various sources of noise limit the dynamic range of elastography. The recently-defined strain filter concept offers an analytical and graphical way of observing these limitations. In this paper, we describe a method that achieves the expansion of the elastographic dynamic range. It involves the application of variable strains in combination with selective storage of strain data that have optimal elastographic signal-to-noise ratios. This expands the current dynamic range of elastography by orders of magnitude when compared to single compression elastography. The process is explained theoretically using the strain filter framework, and 1 D as well as 2D tissue simulations are used to corroborate the theory.

The nonstationary strain filter in elastography: Part II. Lateral and elevational decorrelation.

The nonstationary evolution of the strain filter due to lateral and elevational motion of the tissue scatterers across the ultrasound beam is analyzed for the 1-D cross-correlation-based strain estimator. The effective correlation coefficient that includes the contributions due to lateral and elevational signal decorrelation is used to derate the upper bound of the signal-to-noise ratio in the elastogram (SNRe) predicted by the ideal strain filter. In the case of an elastically homogeneous target, if the transducer is on the axis of symmetry of such target in the elevational direction, the motion of the scatterers out the imaging plane is minimized. In addition, the ultrasound beam along the elevational direction is broader, allowing scatterers to stay longer within the beam during tissue compression. Under these conditions, lateral signal decorrelation becomes the primary contributor to the nonstationary behavior of the strain filter. Both the elastographic SNRe and the dynamic range are reduced, with an increase in lateral decorrelation. Finite element simulations and phantom experiments are presented in this paper to corroborate the theoretical strain filter. The nonstationary behavior of the strain filter is reduced by confining the tissue in the lateral direction (minimizing motion of tissue scatterers), thereby improving the quality of the elastogram.