Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge monitored with three oxygen-sensitive parameters

The simultaneous measurement of three oxygen-sensitive parameters [arterial hemoglobin oxygen saturation (SaO2), tumor vascular-oxygenated hemoglobin concentration ([HbO2]), and tumor oxygen tension (pO2)] in response to hyperoxic respiratory challenge is demonstrated in rat breast tumors. The effects of two hyperoxic gases [oxygen and carbogen (5% CO2 and 95% O2)] were compared, by use of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in pedicles on the foreback. Two different gas-inhalation sequences were compared, i.e., air-carbogen-air-oxygen-air and air-oxygen-air-carbogen-air. The results demonstrate that both of the inhaled, hyperoxic gases significantly improved the tumor oxygen status. All three parameters displayed similar dynamic response to hyperoxic gas interventions, but with different response times: the fastest for arterial SaO2, followed by biphasic changes in tumor vascular [HbO2], and then delayed responses for pO2. Both of the gases induced similar changes in vascular oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2] and mean pO2 showed a linear correlation with large standard deviations, which presumably results from global versus local measurements. Indeed, the pO2 data revealed hetergeneous regional response to hyperoxic interventions. Although preliminary near-infrared measurements had been demonstrated previously in this model, the addition of the pO2 optical fiber probes provides a link between the noninvasive relative measurements of vascular phenomena based on endogenous reporter molecules, with the quantitative, albeit, invasive pO2 determinations.     

Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject

A 1-GHz multifrequency, multiwavelength frequency-domain photon migration instrument is used to measure quantitatively the optical absorption (mu(a)) and effective optical scattering (mu(s) ?) of normal and malignant tissues in a human subject. Large ellipsoidal (~10-cm major axis, ~6-cm minor axes) subcutaneous malignant lesions were compared with adjacent normal sites in the abdomen and back. Absorption coefficients recorded at 674, 811, 849, and 956 nm were used to calculate tissue hemoglobin concentration (oxyhemoglobin, deoxyhemoglobin, and total), water concentration, hemoglobin oxygen saturation, and blood volume fraction in vivo. Our results show that the normal and the malignant tissues measured in the patient have clearly resolvable optical and physiological property differences that may be broadly useful in identifying and characterizing tumors.     

Noninvasive investigation of blood oxygenation dynamics of tumors by near-infrared spectroscopy

The measurement of dynamic changes in the blood oxygenation of tumor vasculature could be valuable for tumor prognosis and optimizing tumor treatment plans. In this study we employed near-infrared spectroscopy (NIRS) to measure changes in the total hemoglobin concentration together with the degree of hemoglobin oxygenation in the vascular bed of breast and prostate tumors implanted in rats. Measurements were made while inhaled gas was alternated between 33% oxygen and carbogen (95% O(2), 5% CO(2)). Significant dynamic changes in tumor oxygenation were observed to accompany respiratory challenge, and these changes could be modeled with two exponential components, yielding two time constants. Following the Fick principle, we derived a simplified model to relate the time constants to tumor blood-perfusion rates. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive means of monitoring the vascular oxygenation dynamics of tumors and facilitate investigations of tumor vascular perfusion. This may have prognostic value and promises insight into tumor vascular development.     

Three-dimensional time-resolved optical mammography of the uncompressed breast

Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.     

Assessment of the size, position, and optical properties of breast tumors in vivo by noninvasive optical methods

We present a method for the noninvasive determination of the size, position, and optical properties (absorption and reduced scattering coefficients) of tumors in the human breast. The tumor is first detected by frequency-domain optical mammography. It is then sized, located, and optically characterized by use of diffusion theory as amodel for the propagation of near-infrared light in breast tissue. Our method assumes that the tumor is a spherical inhomogeneity embedded in an otherwise homogeneous tissue. We report the results obtained on a 55-year-old patient with a papillary cancer in the right breast. We found that the tumor absorbs and scatters near-infrared light more strongly than the surrounding healthytissue. Our method has yielded a tumor diameter of 2.1 ? 0.2cm, which is comparable with the actual size of 1.6 cm, determined after surgery. From the tumor absorption coefficients at two wavelengths (690 and 825 nm), we calculated the total hemoglobin concentration (40 ? 10 muM) and saturation (71 ? 9%) of the tumor. These results can provide the clinical examiner with more detailed information about breast lesions detected by frequency-domain optical mammography, thereby enhancing its potential for specificity.     

Determination of optical parameters of human breast tissue from spatially resolved fluorescence: a diffusion theory model

We report the measurement of optical transport parameters of pathologically characterized malignant tissues, normal tissues, and different types of benign tumors of the human breast in the visible wavelength region. A spatially resolved steady-state diffuse fluorescence reflectance technique was used to estimate the values for the reduced-scattering coefficient (mu(s)') and the absorption coefficient (mu(a)) of human breast tissues at three wavelengths (530, 550, and 590 nm). Different breast tissues could be well differentiated from one another, and different benign tumors could also be distinguished by their measured transport parameters. A diffusion theory model was developed to describe fluorescence light energy distribution, especially its spatial variation in a turbid and multiply scattering medium such as human tissue. The validity of the model was checked with a Monte Carlo simulation and also with different tissue phantoms prepared with polystyrene microspheres as scatterers, riboflavin as fluorophores, and methylene blue as absorbers.     

Classification of ultrasonic B mode images of the breast using frequency diversity and Nakagami statistics

The parameters of the Nakagami distribution have been utilized in the past to classify lesions in breast tissue as benign or malignant. To avoid the effect of operator-gain settings on the parameters of the Nakagami distribution, normalized parameters were utilized for the classification. The normalized parameter was defined as the ratio of the parameter at the site of the lesion to its average value over several regions away from the site. This technique, however, was very time consuming. In this paper, the application of frequency diversity and compounding is explored to achieve this normalization. Lesions are classified using these normalized parameters at the site. A receiver operating characteristic (ROC) analysis of the parameters of the Nakagami distribution has been conducted before and after compounding on a data set of 60 benign and 65 malignant lesions. The ROC results indicate that this technique can reasonably classify lesions in breast tissue as benign or malignant     

Efficient Computer Aided Diagnosis System for Hepatic Tumors Using Computed Tomography Scans

One of the leading causes of mortality worldwide is liver cancer. The earlier the detection of hepatic tumors, the lower the mortality rate. This paper introduces a computer-aided diagnosis system to extract hepatic tumors from computed tomography scans and classify them into malignant or benign tumors. Segmenting hepatic tumors from computed tomography scans is considered a challenging task due to the fuzziness in the liver pixel range, intensity values overlap between the liver and neighboring organs, high noise from computed tomography scanner, and large variance in tumors shapes. The proposed method consists of three main stages; liver segmentation using Fast Generalized Fuzzy C-Means, tumor segmentation using dynamic thresholding, and the tumor's classification into malignant/benign using support vector machines classifier. The performance of the proposed system was evaluated using three liver benchmark datasets, which are MICCAI-Sliver07, LiTS17, and 3Dircadb. The proposed computer adided diagnosis system achieved an average accuracy of 96.75%, sensetivity of 96.38%, specificity of 95.20% and Dice similarity coefficient of 95.13%.     

CXCR‐4 Targeted,Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection

Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare‐earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target‐specific identification of subtissue cancerous lesions.     

成像及波谱成像联合运用对乳腺癌早期诊断的价值

目的:探讨成像及波谱成像联合运用对乳腺癌早期诊断的临床价值。方法:收集我院2012年1月-2013年11月诊治的60例乳腺癌患者,均经siemens(西门子)Avanto1.5T超导磁共振检查。结果:60例经过手术病理或穿刺病理检查确诊良性肿瘤31例,肿瘤直径1.8cm-5.1cm,平均2.9cm,其中纤维腺瘤28例,慢性乳腺炎2例,导管内乳头状瘤1例。乳腺癌29例,肿瘤直径1.1cm-4.6cm,平均2.6cm,其中浸润性导管癌26例,导管原位癌1例,髓样癌1例,浸润性小叶癌1例。31例良性患者中流入型17例,平台型10例,流出型4例,29例恶性患者中流入型4例,平台型9例,流出型16例,两组比较有显著性差异(P0.05)。结论:成像及波谱成像联合运用对乳腺癌早期诊断有着重要的临床意义,值得临床推广。     

探讨高频超声检测乳腺肿块内不同钙化类型在诊断乳腺癌中的价值

目的:探讨高频超声检测乳腺肿块内不同钙化类型在诊断乳腺癌中的价值和重要性.方法:采用高频超声探头显像特征和内部回声等声像图对乳腺癌患者进行肿块病理结果分析.结果:手术后经过病理检查可知,高频超声诊断的符合率达到98％.其中肿块内不同钙化点类型对于鉴别良恶性诊断极为重要.结论:对于乳腺癌高频超声具有较好的诊断价值,利用高频超声检测乳腺肿块内不同钙化类型可以明显提高乳腺癌的诊断率,具有重要的临床应用价值.     

Quantitative oximetry of breast tumors: a near-infrared method that identifies two optimal wavelengths for each tumor

We present a noninvasive optical method to measure the oxygen saturation of hemoglobin in breast lesions. This method introduces the novel concept that the best choice of near-infrared wavelengths for noninvasive tumor oximetry consists of a wavelength pair (lambda1, lambda2) within the range 680-880 nm, where the specific values of lambda1 and lambda2 depend on the optical properties of the specific tumor under examination. Our method involves two steps: (1) identify the optimal wavelength pair for each tumor and (2) measure the tumor oxygenation using the optical data at the two selected wavelengths. We have tested our method by acquiring experimental optical data from turbid media containing cylindrical or irregularly shaped inhomogeneities and by computing theoretical data for the case of spherical lesions embedded in a highly scattering medium. We have found that our optical method can provide accurate and quantitative measurements of the oxygenation of embedded lesions without requiring knowledge of their size, shape, and depth.     

Dynamic plastic response of a circular plate based on unified strength theory

The study and design of structures under dynamic loads require a knowledge of the plastic response and deformation behavior under impact loading. The calculations of dynamic plastic response of structures are useful for the design and investigation of colliding vehicle, engine and various impacting structures. The unified solutions of dynamic plastic load-carrying capacities, moment fields and velocity fields of a simply supported circular plate are introduced. The strength is different in tension and compression and the effect on the yield criteria is taken into account by using the unified strength theory. Upper bound and lower bound plastic responses of the plate, under moderate partial uniformly distributed impulsive loading, are obtained. The static and kinematical admissibility of the dynamic plastic solutions are discussed. The unified solutions of the static plastic load-carrying capacities, moment fields and velocity fields of a simply supported circular plate are also obtained according to the dynamic solutions in this paper. The solutions are suitable for many materials with or without different strengths in tension and compression and the effect of intermediate principal stress.The solutions based on the Tresca, the von Mises, the Mohr–Coulomb theory, and the twin-shear strength theory, as well as the unified yield criterion, are all the special cases of the unified solutions. The influences of the coefficient of failure criteria, b, and tension-compression strength ratio, α, on the dynamic and static solutions, are investigated. It is shown that the effects of different strengths in tension and compression and yield criteria on the dynamic load-carrying capacity are greater than in the static plastic limit state.     

The Fibrillar Matrix: Novel Avenues for Breast Cancer Detection and Treatment

Breast cancer is marked by large increases in the protein fibers around tumor cells. These fibers increase the mechanical stiffness of the tissue, which has long been used for tumor diagnosis by manual palpation. Recent research in bioengineering has led to the development of novel biomaterials that model the mechanical and architectural properties of the tumor microenvironment and can be used to understand how these cues regulate the growth and spread of breast cancer. Herein, we provide an overview of how the mechanical properties of breast tumor tissues differ from those of normal breast tissue and non-cancerous lesions. We also describe how biomaterial models make it possible to understand how the stiffness and viscosity of the extracellular environment regulate cell migration and breast cancer metastasis. We highlight the need for biomaterial models that allow independent analysis of the individual and different mechanical properties of the tumor microenvironment and that use cells derived from different regions within tumors. These models will guide the development of novel mechano-based therapies against breast cancer metastasis.     

Performance analysis of brain tissues and tumor detection and grading system using ANFIS classifier

Abnormal growth of cells in brain leads to the formation of tumors, which are categorized into benign and malignant. In this article, Co‐Active Adaptive Neuro Fuzzy Inference System (CANFIS) classification based brain tumor detection and its grading system is proposed. It has two phases as brain tumor segmentation and brain tissue segmentation. In brain tumor segmentation, CANFIS classifier is used to classify the test brain image into benign or malignant. Then, morphological operations are applied over the malignant image in order to segment the tumor regions in brain image. The K‐means classifier is used to classify the brain tissues into Grey Matter (GM), White Matter (WM) and Cerebro Spinal Fluid (CSF) regions as three different classes. Next, the segmented tumor is graded as mild, moderate or severe based on the presence of segmented tumor region in brain tissues.     

Spectroscopic diffuse optical tomography for the quantitative assessment of hemoglobin concentration and oxygen saturation in breast tissue

Near-infrared (NIR) spectroscopic diffuse tomography has been used to map the hemoglobin concentration and the hemoglobin oxygen saturation quantitatively in tissuelike phantoms and to determine average values in vivo. A series of phantom calibrations were performed to achieve quantitatively accurate images of the absorption and the reduced scattering coefficients at multiple optical wavelengths. A least-squares fit was applied to absorption-coefficient images at multiple NIR wavelengths to obtain hemoglobin images of the concentration and the hemoglobin oxygen saturation. Objects of varying hemoglobin concentration and oxygen saturation within highly scattering media were localized and imaged to within 15% of their actual values. The average hemoglobin concentration and oxygen saturation of breast tissue was measured in vivo for two women volunteers. The potential application for the diagnosis of breast tumors is discussed.     

Classification of ultrasonic B-mode images of breast masses using Nakagami distribution

The Nakagami distribution was proposed recently for modeling the echo from tissue. In vivo breast data collected from patients with lesions were studied using this Nakagami model. Chi-square tests showed that the Nakagami distribution is a better fit to the envelope than the Rayleigh distribution. Two parameters, m (effective number) and α (effective cross section), associated with the Nakagami distribution were used for the classification of breast masses. Data from 52 patients with breast masses/lesions were used in the studies. Receiver operating characteristics were calculated for the classification methods based on these two parameters. The results indicate that these parameters of the Nakagami distribution may be useful in classification of the breast abnormalities. The Nakagami distribution may be a reasonable means to characterize the backscattered echo from breast tissues toward a goal of an automated scheme for separating benign and malignant breast masses     

常规超声联合声触诊组织定量技术诊断乳腺肿块的价值

探讨常规超声联合声触诊组织定量技术(Virtual Touch tissue Quantification,VTQ)在鉴别诊断乳腺良恶性肿块中的应用价值。自2014年2月至2015年6月期间收集同济大学附属第十人民医院385例患者共387个肿块,对各病灶进行声触诊组织定量检测,获取乳腺肿块VTQ值,肿块良恶性以病理(穿刺活检/手术切除)结果为金标准,构建ROC曲线,判断诊断价值。常规超声的敏感性、特异性、准确性分别为72.59%、84.27%、81.34%。VTQ的敏感性、特异性、准确性分别为80.11%、90.37%、87.21%。常规超声联合VTQ的敏感性、特异性、准确性分别为80.52%、92.44%、92.32%。常规超声联合声触诊组织定量技术能够提高诊断的敏感性、特异性和准确性,有助于乳腺良恶性肿块的鉴别诊断。     

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.     

Adrenal tumor characterization on magnetic resonance images

Adrenal tumors occur on adrenal glands and are generally detected on abdominal area scans. Adrenal tumors, which are incidentally detected, release vital hormones. These types of tumors that can be malignant affect body metabolism. Both of benign and malign adrenal tumors can have a similar size, intensity, and shape, this situation may lead to wrong decision during diagnosis and characterization of tumors. Thus, biopsy is done to confirm diagnosis of tumor types. In this study, adrenal tumor characterization is handled by using magnetic resonance images. In this way, it is wanted that patient can be disentangled from one or more imaging modalities (some of them can includes X-ray) and biopsy. An adrenal tumor image set, which includes five types of adrenal tumors and has 112 benign tumors and 10 malign tumors, was used in this study. Two data sets were created from the adrenal tumor image set by manually/semiautomatically segmented adrenal tumors and feature sets of these data sets are constituted by different methods. Two-dimensional gray-level co-occurrence matrix (2D-GLCM), gray-level run-length matrix (GLRLM), and two-dimensional discrete wavelet transform (2D-DWT) methods were analyzed to reveal the most effective features on adrenal tumor characterization. Feature sets were classified in two ways: benign/malign (binary classification) and type characterization (multiclass classification). Support vector machine and artificial neural network classified feature sets. The best performance on benign/malign classification was obtained by the 2D-GLCM feature set. The best results were assessed with sensitivity, specificity, accuracy, precision, and F-score metrics and they were 99.17%, 90%, 98.4%, 99.17%, and 99.13%, respectively. The highest classification performance on type characterization was obtained by the 2D-DWT feature set as 59.62%, 96.17%, 93.19%, 54.69%, and 54.94% for sensitivity, specificity, accuracy, precision, and F-score metrics, respectively.