A cadaveric breast cancer tissue phantom for phase-contrast X-ray imaging applications

Background : As mammography X-ray imaging technologies advance and provide elevated contrast in soft tissues, a need has developed for reliable imaging phantoms for use in system design and component calibration. In advanced imaging modalities such as refraction-based methods, it is critical that developed phantoms capture the biological details seen in clinical precancerous and cancerous cases while minimizing artifacts that may be caused due to phantom production. This work presents the fabric...     

Model-based ultrasound tomography: tissue phantom experiments

We present a detailed experimental study to evaluate our finite element based nonlinear reconstruction algorithm for recovery of acoustic properties in heterogeneous scattering media. Using a circularly scanning ultrasound system at 500 KHz, tissue phantom experiments were performed to study spatial resolution and contrast issues in model-based ultrasound tomography. Our results show that both acoustic attenuation and speed images can be quantitatively reconstructed in terms of the location, size, shape, and acoustic property value of the target when different contrast levels between the target and background were used. We also demonstrate that a high contrast target as small as 3 mm in diameter can be quantitatively resolved with our acoustic speed and attenuation images.     

Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies

Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm(3) single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8x8x8 cm(3)) in response to area illumination (12 cm(2)) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.     

Helical antenna arrays for interstitial microwave thermal therapy for prostate cancer: tissue phantom testing and simulations for treatment

Interstitial microwave therapy is an experimental treatment for prostate cancer. The objective of this work was to measure the power deposition (specific absorption rate, SAR) patterns of helical microwave antennae both individually and in array patterns that would be useful for clinical treatment protocols. Commercial helical antenna 3D SAR patterns were measured in muscle equivalent phantoms using a thermographic technique. Two array patterns were tested: a 'square' and a 'crescent' array, both surrounding the urethra. To assess the feasibility of pre-treatment planning, the measured SAR patterns were input to a treatment planning computer simulation program based on a series of trans-rectal ultrasound images from a prostate cancer patient. The simulation solved the Pennes linear bioheat heat transfer equation in prostate tissue, with the aim of achieving a target of 55 degrees C at the prostate periphery while not allowing normal surrounding tissues (bladder, urethra, rectum) to rise above 42 C. These criteria could not be met with the square array but they could be met with the crescent array, provided that the prostate was first dissected away from the rectum. This can be done with a procedure such as 'hydrodissection', where sterile saline is injected to separate the prostate and rectum. The results of these SAR measurements and heat transfer simulations indicate that arrays of helical antennae could be used for safe and effective thermal therapy for prostate cancer.     

B超引导下微波热毁损治疗肝脏海绵状血管瘤

目的观察微波热毁损治疗肝脏海绵状血管瘤的疗效及安全性。方法87例肝脏海绵状血管瘤患者，其中男性28例，女性59例，平均年龄42．6岁。113个病灶，瘤体直径5～10cm。在B超引导下采用微波治疗肝脏单发及多发海绵状血管瘤。结果3个月后复查B超，68个病灶（≤8cm）瘤体体积缩小50％以上，瘤体血供全部消失，病灶完全毁损；其余病灶瘤体体积缩小25％以上，病灶内血流明显减少。6个月后复查，仅3个直径≥8cm的病灶体积增大，经第2次治疗后血流消失。全部病例无出血等并发症。结论B超引导下经皮肝穿刺微波热毁损治疗肝脏血管瘤，安全有效，无并发症；对≥8cm的病灶需2次以上治疗才能达到满意疗效。     

医学影像仿真人体模型及其临床应用

仿真人体模型是根据人体参数,用与人体组织具有相同或相近散射和吸收系数的“组织等效材料”制成的具有骨骼、肌肉、脏器的人体模型。它包括数字化虚拟人体模型、物理实体模型和二者结合的物理数学模型等3种类型。仿真体模在临床工作中应用广泛,可用于确定CT扫描方式及最佳扫描方案、优化患者的辐射剂量、设备评价及质量控制以及用于血管成像和对比剂注射方案研究。仿真体模模拟人体参数能避免不必要的辐射危害,未来在CT图像质控、设备评价、方案研究等方面前景十分可观。     

Acoustical properties of selected tissue phantom materials for ultrasound imaging

This note summarizes the characterization of the acoustic properties of four materials intended for the development of tissue, and especially breast tissue, phantoms for the use in photoacoustic and ultrasound imaging. The materials are agar, silicone, polyvinyl alcohol gel (PVA) and polyacrylamide gel (PAA). The acoustical properties, i.e., the speed of sound, impedance and acoustic attenuation, are determined by transmission measurements of sound waves at room temperature under controlled conditions. Although the materials are tested for application such as photoacoustic phantoms, we focus here on the acoustic properties, while the optical properties will be discussed elsewhere. To obtain the acoustic attenuation in a frequency range from 4 MHz to 14 MHz, two ultrasound sources of 5 MHz and 10 MHz core frequencies are used. For preparation, each sample is cast into blocks of three different thicknesses. Agar, PVA and PAA show similar acoustic properties as water. Within silicone polymer, a significantly lower speed of sound and higher acoustical attenuation than in water and human tissue were found. All materials can be cast into arbitrary shapes and are suitable for tissue-mimicking phantoms. Due to its lower speed of sound, silicone is generally less suitable than the other presented materials.     

Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies

For real-time optoacoustic (OA) imaging of the human body, a linear array transducer and reflection mode optical irradiation is usually preferred. Such a setup, however, results in significant image background, which prevents imaging structures at the ultimate depth determined by the light distribution and the signal noise level. Therefore, we previously proposed a method for image background reduction, based on displacement-compensated averaging (DCA) of image series obtained when the tissue sample under investigation is gradually deformed. OA signals and background signals are differently affected by the deformation and can thus be distinguished. The proposed method is now experimentally applied to image artificial tumours embedded inside breast phantoms. OA images are acquired alternately with pulse-echo images using a combined OA/echo-ultrasound device. Tissue deformation is accessed via speckle tracking in pulse echo images, and used to compensate in the OA images for the local tissue displacement. In that way, OA sources are highly correlated between subsequent images, while background is decorrelated and can therefore be reduced by averaging. We show that image contrast in breast phantoms is strongly improved and detectability of embedded tumours significantly increased, using the DCA method.     

X-ray properties of an anthropomorphic breast phantom for MRI and x-ray imaging

The purpose of this study is to characterize the x-ray properties of a dual-modality, anthropomorphic breast phantom whose MRI properties have been previously evaluated. The goal of this phantom is to provide a platform for optimization and standardization of two- and three-dimensional x-ray and MRI breast imaging modalities for the purpose of lesion detection and discrimination. The phantom is constructed using a mixture of lard and egg whites, resulting in a variable, tissue-mimicking structure with separate adipose- and glandular-mimicking components. The phantom can be produced with either a compressed or uncompressed shape. Mass attenuation coefficients of the phantom materials were estimated using elemental compositions from the USDA National Nutrient Database for Standard Reference and the atomic interaction models from the Monte Carlo code PENELOPE and compared with human values from the literature. The image structure was examined quantitatively by calculating and comparing spatial covariance matrices of the phantom and patient mammography images. Finally, a computerized version of the phantom was created by segmenting a computed tomography scan and used to simulate x-ray scatter of the phantom in a mammography geometry. Mass attenuation coefficients of the phantom materials were within 20% and 15% of the values for adipose and glandular tissues, respectively, which is within the estimation error of these values. Matching was improved at higher energies (>20 keV). Tissue structures in the phantom have a size similar to those in the patient data, but are slightly larger on average. Correlations in the patient data appear to be longer than those in the phantom data in the anterior-posterior direction; however, they are within the error bars of the measurement. Simulated scatter-to-primary ratio values of the phantom images were as high as 85% in some areas and were strongly affected by the heterogeneous nature of the phantom. Key physical x-ray properties of the phantom have been quantitatively evaluated and shown to be comparable to those of breast tissue. Since the MRI properties of the phantom have been previously evaluated, we believe it is a useful tool for quantitative evaluation of two- and three-dimensional x-ray and MRI breast imaging modalities for the purpose of lesion detection and characterization.     

Comparisons of three alternative breast modalities in a common phantom imaging experiment

Four model-based imaging systems are currently being developed for breast cancer detection at Dartmouth College. A potential advantage of multimodality imaging is the prospect of combining information collected from each system to provide a more complete diagnostic tool that covers the full range of the patient and pathology spectra. In this paper it is shown through common phantom experiments on three of these imaging systems that it was possible to correlate different types of image information to potentially improve the reliability of tumor detection. Imaging experiments were conducted with common phantoms which mimic both dielectric and optical properties of the human breast. Cross modality comparison was investigated through a statistical study based on the repeated data sets of reconstructed parameters for each modality. The system standard error between all methods was generally less than 10% and the correlation coefficient across modalities ranged from 0.68 to 0.91. Future work includes the minimization of bias (artifacts) on the periphery of electrical impedance spectroscopy images to improve cross modality correlation and implementation of the multimodality diagnosis for breast cancer detection.     

Evaluation of proton density by magnetic resonance imaging: phantom experiments and analysis of multiple component proton transverse relaxation

The quantitative evaluation of proton density by magnetic resonance imaging (MRI) is limited as a result of non-uniformities in the intensity distribution of the images and by the fact that only part of the protons of the tissue contribute to the image signal. This study was undertaken to estimate the accuracy of proton density measurements using a standard whole-body MR imager operating at 1.5 T. First, phantom experiments were performed to examine the possibility of an intensity correction. For the test phantom the systematical errors in the computed proton densities were reduced from 5 to 1% after correction. Secondly, proton transverse relaxation curves of biological tissues were measured in vitro on an MR spectrometer. A multi-exponential analysis of the data shows that for spin-echo times TE greater than 10 ms in total between 10 and 30% of the protons of the tissue do not contribute to the image signal. In all tissues a proton component with a free induction decay (FID) time T2* less than 32 microseconds was observed. In the time range TE greater than 10 ms two proton components can be distinguished in muscle and fatty tissue. Finally, it will be shown that a pixel-orientated two-exponential analysis of spin-echo images leads to a much more homogeneous density image than one-exponential computation, since tissue-specific biexponentiality and partial volume effects are taken into account. As a conclusion, the hydrogen density of biological tissues can be evaluated at best with an overall error of 10% from MR images for TE greater than 10 ms. This accuracy is insufficient for a pixel-orientated neutron therapy planning.     

乳腺癌组织中IL-6与PRL表达及其临床意义

目的　探讨白介素-6（interleukin-6,IL-6）和催乳素（prolactin,PRL）在乳腺浸润性导管癌（breast invasive ductal carcinoma,BIDC）组织中的表达及临床意义。 方法　采用免疫组化法对63例乳腺癌及其癌旁组织、17例乳腺纤维瘤中IL-6和PRL的表达进行检测,结合临床病理参数及无事件生存（event free survival,EFS）进行统计学分析。 结果　浸润性导管癌组织中IL-6和PRL阳性率均高于癌旁组织及乳腺纤维瘤组织（P均＜0.05）;癌旁组织中IL-6和PRL的表达高于瘤旁组织（P均＜0.05）;IL-6、PRL的表达均与肿瘤大小、TNM分期相关（P均＜0.05）;IL-6与PRL表达呈显著正相关（rs=0.842,P＜0.05）。EFS显示,IL-6、PRL高表达组患者EFS均低于低表达组患者（分别为IL-6,Log- rank= 5.186,P= 0.023;PRL, Log- rank= 5.743,P= 0.017）。单因素Cox风险模型显示,淋巴结转移、TNM分期高、IL-6阳性表达、PRL阳性表达均对患者的EFS有影响。 结论　检测乳腺癌中PRL和IL-6的表达有利于其预后诊断;通过缓解病人的紧张、促进情绪调节、改善睡眠质量等因素可在一定程度上降低乳腺癌的发生、进展及不良预后的风险。     

Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms

We present a laboratory version of a photoacoustic mammoscope, based on a parallel plate geometry. The instrument is built around a flat high-density ultrasound detector matrix. The light source is a Q-switched Nd:YAG laser with a pulse duration of 5 ns. To test the instrument, a novel photoacoustic phantom is developed using poly(vinyl alcohol) gel, prepared by a simple procedure that imparts optical scattering suggestive of breast tissue to it without the requirement for extraneous scattering particles. Tumor simulating poly(vinyl alcohol) gel spheres appropriately dyed at the time of preparation are characterized for optical absorption coefficients. These are then embedded in the phantom to serve as tumors with absorption contrasts ranging from 2 to 7, with respect to the background. Photoacoustic studies in transmission mode are performed, by acquiring the laser-induced ultrasound signals from regions of interest in the phantom. Image reconstruction is based on a delay-and-sum beamforming algorithm. The results of these studies provide an insight into the capabilities of the prototype. Various recommendations that will guide the evolving of our laboratory prototype into a clinical version are also discussed.     

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood–brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics—particularly those targeted to cross the BBB—as well as detection of small nonpermeable metastases.     

Molecular and functional imaging of breast cancer

Despite several major advances in breast cancer diagnosis and treatment, the American Cancer Society has estimated that in the US alone 43300 women and 400 men will die from breast cancer in 2007. Breast cancer typically is a multi-focal, multi-faceted disease, with the major cause of mortality being complications due to metastasis. Whereas a decade ago genetic alterations were the primary focus in cancer research, it is now apparent that the physiological tumor microenvironment, interactions between cancer cells and stromal cells such as endothelial cells, fibroblasts and macrophages, the extracellular matrix, and a multitude of secreted factors and cytokines influence progression, aggressiveness, and response of the disease to treatment. Prevention, early diagnosis, and treatment are the three broad challenges for MR molecular and functional imaging in reducing mortality from this disease. Multi-parametric molecular and functional MRI provides unprecedented opportunities for identifying novel targets for imaging and therapy at the bench, as well as for accurate diagnosis and monitoring response to therapy at the bedside. Here we provide an overview of the current status of molecular and functional MRI of breast cancer, outlining some key developments, as well as identifying some of the important challenges facing this field in the future.     

Experimental validation of a radiographic simulation code using breast phantom for X-ray imaging

Computer models and simulations of X-ray imaging systems are becoming a very precious tool during the development and evaluation of new X-ray imaging techniques. To provide, however, a faithful simulation of a system, all components must be accurately modelled and tested, followed by verification through experimental measurements. This paper presents a validation study of the XRayImagingSimulator, an in-house developed X-ray imaging simulator, which is extensively used as a basic tool in carrying out complex breast imaging simulations. The approach followed compares results obtained via an experimental setup for breast phantom (CIRS 011A) imaging, using synchrotron radiation (SYRMEP beamline at ELETTRA), with those from its simulated setup under the same conditions. The study demonstrated a very good agreement between experimental and simulated images compared both in terms of subjective and objective criteria. The combination of the XRayImagingSimulator with our BreastSimulator provides a powerful tool for in silico testing of new X-ray breast imaging approaches.     

Reflected light intensity profile of two-layer tissues: phantom experiments

Experimental measurements of the reflected light intensity from two-layer phantoms are presented. We report, for the first time, an experimental observation of a typical reflected light intensity behavior for the two-layer structure characterized by two different slopes in the reflected light profile of the irradiated tissue. The point in which the first slope changes to the second slope, named as the crossover point, depends on the upper layer thickness as well as on the ratio between the absorption coefficients of the two layers. Since similar experiments from one-layer phantoms present a monotonic decay behavior, the existence and the location of the crossover point can be used as a diagnostic fingerprint for two-layer tissue structures. This pertains to two layers with greater absorptivity in the upper layer, which is the typical biological case in tissues like skin.