基于电阻抗扫描的乳腺组织阻抗频谱特性测量实验

为了研究乳腺组织电导率特性及肿瘤生长方式对电阻抗扫描(electrical impedance scanning,EIS)肿瘤成像特征的影响,作者对照分析了69例乳腺肿瘤患者的EIS成像、X线钼靶摄影及离体乳腺组织的阻抗频谱特性。实验得到了40例恶性肿瘤、34例良性肿瘤、49例腺体组织和41例脂肪组织的离体电阻率特性,其中腺体组织和良性肿瘤的电阻率数值最小,其次是癌组织,脂肪组织的电阻率数值最大。恶性肿瘤中EIS检查24例高亮表现,11例暗区表现,5例无表现;良性肿瘤EIS检查多数无特征表现。实验表明,癌组织与其周围正常组织的电导率有显著性差异。因恶性肿瘤浸润组织的不同,组织间的电导率差异会出现正向或负向变化,EIS检查表现出亮、暗不同的特征成像。良性肿瘤的电导率较好,但其与周围组织电导率差异无统计学意义,EIS检查无显著成像。     

Some early results related to electrical impedance of normal and abnormal gastric tissue

Gastric cancer is the fourth most common cancer and most patients with gastric cancer are being diagnosed in advanced stages of the disease so they do not gain any survival chance from conventional surgical, chemotherapeutic or radiotherapeutic methods. These are relatively high cost procedures in terms of both time and money. This study considers the introduction of a novel minimally invasive diagnostic technique which shows the relationship between histopathology and the electrical impedance spectrum in the human stomach. In this study, 4 electrode technique was used to differentiate tissues from each other using Tabriz Mark 1 electrical impedance system (30 different frequencies in the range of 2 kHz to 1 MHz). A total of 97 points from 45 patients were studied in terms of their biopsy reports matching to the electrical impedance measurements (in vivo). After impedance measurements and applying calibration factors, a non-parametric statistical technique, the Kruskal–Wallis test was used to evaluate the difference among the groups. According to the calculation of respective data using this spectroscopy system, the resistivity of the normal group was higher than that of the benign group, and the resistivity of these groups were higher than that of the malignant group at frequencies between 470 kHz and 1 MHz (P < 0.05). In these frequencies, the impedivity of the dysplastic tissue was significantly lower than that of the other groups (P < 0.05). Also, Cole equation fitting procedure was used to generate a scatter plot of the malignant and benign points: it shows in general, benign points had higher values of R than the malignant points. Therefore, electrical impedance spectroscopy can be a useful technique to characterize the stomach tissue.     

Dynamic Impedance Model of the Skin-Electrode Interface for Transcutaneous Electrical Stimulation

Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.     

In vivo electrical impedance spectroscopic monitoring of the progression of radiation-induced tissue injury.

This study evaluates the potential of electrical impedance spectroscopy (EIS) as a noninvasive technique for tracking the progression of radiation-induced damage in normal muscle tissue. Male Sprague-Dawley rats were irradiated locally to the gastrocnemius and biceps femoris muscle. Single doses were administered using a procedure that spares skin and bone. Complex impedance spectral measurements (taken at 50 frequency points between 1 kHz and 1 MHz) were made at monthly intervals using recessed disk electrodes applied to the skin. A histological scoring scheme was developed for evaluation of injury. A strong dose-dependent progression of injury evident in both spectral measurements and histological scoring has been observed. Latent time also appears to be dependent on dose with changes induced by 70 Gy evident by 2 months, changes induced by 90 Gy observed by 1 month, and dramatic changes found within 3 weeks at 150 Gy. Injury was morphologically comparable to the type of damage that occurs in response to small, fractionated doses, but on a much shorter time scale. Increased spectral shift was a consistent indicator of the extent of tissue injury at the time of measurement. The use of a large single dose resulted in an excellent model in terms of inducing a significant progression in tissue injury over a short post-treatment follow-up period in the muscle mass while also providing a consistent location for in vivo electrical impedance measurements. The results show that EIS can follow radiation-induced tissue change, suggesting that EIS has the potential to monitor the types of injury observed in late radiation damage of muscle tissue noninvasively.     

Newly explored electrical properties of normal skin and special skin sites.

Skin impedance measurements at various skin sites yield different impedance loci for normal skin and special skin sites. The results of skin impedance measurements taken at such sites with a two-electrode measurement system are presented herein. Some of these sites can be identified as acupuncture points. Data from 4 volunteers were acquired by means of a data acquisition board and a measuring system consisting of the measurement circuit, including several electrode types, and a power supply. The Cole model is a model for an equivalent electrical circuit of the skin-electrode system. The system was used to derive skin-typical parameters from the Bode plot of the whole system. These parameters are the fractional power a, the pseudo-capacity K, the parallel resistance Rp, and the serial resistance Rs of the equivalent electrical circuit. The results show that the measured parameters differ between normal skin and special skin sites. These effects have not previously been discovered by other authors, since there has been no systematic investigation of many acupuncture points to date, and there has been no apparent need for such an investigation. A number of necessary criteria for acupuncture point detection can be derived from the results obtained.     

Numerical sensitivity modeling for the detection of skin tumors by using tetrapolar probe

The measurement of electrical impedance of skin using surface electrodes permits the assessment of changes in local properties of the skin and can be used in the detection of tumors. The sensitivity of this technique depends mainly on the geometry of the probe and the size of the tumor. In this article, the impedance method was used to estimate the sensitivity of a tetrapolar probe in detecting small regions of increased conductivity in a stratified model of human skin. The impedance method was used to model the potential distribution using fasorial analysis to solve the node equations of the equivalent circuit. Interpolation was applied to reduce discretization error. The skin was modeled as a three-layer structure with different conductivity and permittivity obtained from the literature. A tumor was modeled as a small volume with admittivity four times higher than the normal tissue. Sensitivity calculation was made as a function of electrode diameter and separation, tumor size, and excitation frequency. The simulations indicated that by inserting a one square millimeter tumor in the epidermis, the load impedance to the current source varies about 1% while the transfer impedance varied 8%. The sensitivity also increases nonlinearly with increasing tumor area and thickness. Additionally, it was found that the sensitivity of the transfer impedance has a maximum value when the electrodes are separated by 1.8?mm. The results show that transfer impedance measurements of the skin may detect small skin tumors with a reasonable sensitivity by using an appropriate tetrapolar probe.     

Numerical sensitivity modeling for the detection of skin tumors by using tetrapolar probe

The measurement of electrical impedance of skin using surface electrodes permits the assessment of changes in local properties of the skin and can be used in the detection of tumors. The sensitivity of this technique depends mainly on the geometry of the probe and the size of the tumor. In this article, the impedance method was used to estimate the sensitivity of a tetrapolar probe in detecting small regions of increased conductivity in a stratified model of human skin. The impedance method was used to model the potential distribution using fasorial analysis to solve the node equations of the equivalent circuit. Interpolation was applied to reduce discretization error. The skin was modeled as a three-layer structure with different conductivity and permittivity obtained from the literature. A tumor was modeled as a small volume with admittivity four times higher than the normal tissue. Sensitivity calculation was made as a function of electrode diameter and separation, tumor size, and excitation frequency. The simulations indicated that by inserting a one square millimeter tumor in the epidermis, the load impedance to the current source varies about 1% while the transfer impedance varied 8%. The sensitivity also increases nonlinearly with increasing tumor area and thickness. Additionally, it was found that the sensitivity of the transfer impedance has a maximum value when the electrodes are separated by 1.8 mm. The results show that transfer impedance measurements of the skin may detect small skin tumors with a reasonable sensitivity by using an appropriate tetrapolar probe.     

Immunochemical study of estrogen-binding alpha-globulin in the tissues and blood serum of cancer patients

EBA distribution in tumour and normal tissues was investigated using immunochemical method. The antigen was found in spleen, kidney and mammary gland extracts, as well as in the extracts of the malignant stomach tissue, throat, kidney, urinary bladder, testicles, i.e. this antigen can be secreted into blood in some forms of malignant neoplasia and is, consequently, a tumour-associated antigen. Further investigations will show, if this protein can be used for the diagnosis of malignant diseases.     

用组织光学特性鉴别诊断人离体的正常膀胱和膀胱癌组织

研究正常人膀胱和膀胱癌组织在Kube lka-Munk二流模型下对476.5 nm,514.5 nm和808 nm波长的激光的光学特性的差异。采用双积分球系统和Kube lka-Munk二流模型进行测量研究。实验结果表明,正常膀胱和膀胱癌组织在Kube lka-Munk二流模型下对476.5 nm,514.5 nm和808 nm波长的每一个波长的激光的吸收、散射、总衰减、有效衰减系数都有非常显著性的差异(P<0.01)。膀胱癌组织对476.5 nm,514.5 nm和808nm波长的激光的吸收系数明显地较正常膀胱组织对相应波长的激光的吸收系数要大(P<0.01),膀胱癌组织对476.5 nm和514.5 nm波长的激光的散射系数明显地较正常膀胱组织对相应波长的激光的散射系数要小(P<0.01),而膀胱癌组织对808 nm波长的激光的散射系数明显地较正常膀胱组织对同一波长的激光的散射系数要大(P<0.01)。膀胱癌组织对476.5 nm,514.5 nm和808 nm波长的激光的总衰减系数明显地较正常膀胱组织对相应波长的激光的总衰减系数要大(P<0.01),膀胱癌组织对476.5 nm,514.5 nm和808 nm波长的激光的有效衰减系数明显地较正常膀胱组织对相应波长的激光的有效衰减系数要大(P<0.01)。提示使用双积分球系统和Kube lka-Munk二流模型来确定离体的正常膀胱组织和膀胱癌组织对476.5 nm,514.5 nm和808nm波长的激光的光学特性的差异鉴别诊断病变的膀胱组织是一个有效的方法。     

Lack of Decorin Expression by Human Bladder Cancer Cells Offers New Tools in the Therapy of Urothelial Malignancies

Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demonstrated using the publicly available GeneSapiens databank that decorin gene expression is present in both normal and malignant human bladder tissues. However, when we applied in situ hybridization with digoxigenin-labeled RNA probes for decorin on human bladder carcinoma tissue samples derived from a large radical cystectomy patient cohort (n = 199), we unambiguously demonstrated that invasive and non-invasive bladder carcinoma cells completely lack decorin mRNA. The cancer cells were also negative for decorin immunoreactivity. Instead, decorin expression was localized solely to original non-malignant stromal areas of bladder tissue. In accordance with the aforementioned results, human bladder cancer cells in vitro were also negative for decorin expression as shown by RT-qPCR analyses. The lack of decorin expression by bladder cancer cells was shown not to be due to the methylation of the proximal promoter region of the decorin gene. When bladder cancer cells were transfected with a decorin adenoviral vector, their proliferation was significantly decreased. In conclusion, we have shown that human bladder cancer cells are totally devoid of decorin expression. We have also shown that adenovirus-mediated decorin gene transduction of human bladder cancer cell lines markedly inhibits their proliferation. Thus, decorin gene delivery offers new potential therapeutic tools in urothelial malignancies.     

Immunohistochemical detection of nucleolar protein p120 in paraffin-embedded tissues

The monoclonal antibody FB-2 recognizes the antigen p120-kDa protein (p120), associated with the nucleolar matrix. p120 has originally been reported as expressed and detectable in malignant and non-neoplastic proliferating cells, but not in most normal resting tissues and benign tumours. In the present study, a reliable immunostaining method was used to detect p120 on formalin-fixed, paraffin wax-embedded tissue, testing it on 148 samples from different neoplastic and non-neoplastic tissues from different organs (breast, colon, lung, prostate, bladder, lymph nodes, skin, tongue and liver). The immunostaining was performed after the application of a specific antigen-unmasking protocol based on six consecutive cycles of microwave oven heating. Under these retrieval conditions, p120 antigen was clearly detectable, not only in hyperplastic and malignant cells, but also in stromal and normal non-proliferating cells of all the tissues evaluated. Our results show that the nucleolar protein p120 can be detected by routine immunohistochemistry in formalin-fixed, paraffin-embedded tissue and is expressed in all nucleated cells under any biological condition. This revised version was published online in November 2006 with corrections to the Cover Date.     

A measuring device for calculating electrical impedance of the heart in clinical conditions]

Changes in the electrical impedance of tissue can indicate structural changes. This suggests a technique for the noninvasive detection of allograft rejection after heart transplantation. The direct electrical connection to the heart and the application of a measuring current to the myocardium requires a high standard of safety. A device was developed for measuring cardiac impedance using a sinusoidal current of 20 microA at a frequency of 15 kHz. The control logic ensures a slow current onset and also an immediate cessation in case of conductor fracture or excessive voltage. Initial results in patients with normal recovery after heart transplantation revealed a rapid drop in impedance to about 70% of the initial value in the 1st 48 hours and then a stable course. In the sole rejection episode observed so far, the impedance increased again to 85% of the initial value. This paper discusses the technical safety requirements and the design of the device, and presents initial results of clinical examinations.     

532 nm和808 nm激光及其线偏振激光辐照人正常膀胱与膀胱癌组织光学特性

采用双积分球系统和光辐射测量技术的基本原理 ,以及运用生物组织的光学模型 ,研究了 5 32nm和80 8nm激光及其线偏振激光辐照人正常膀胱和膀胱癌组织的光学特性 .结果表明 :膀胱癌组织对同一波长的激光或其线偏振激光的衰减明显较正常膀胱组织的要大 ,膀胱癌组织对 5 32nm和 80 8nm激光的衰减均较其线偏振激光的要略大一些 .膀胱癌组织对 5 32nm和 80 8nm激光及其线偏振激光的衰减明显较正常膀胱组织的要大 .正常膀胱或膀胱癌组织对同一波长的激光及其线偏振激光的折射率均没有明显的差异 ,膀胱癌组织对 5 32nm和80 8nm激光的折射率比正常膀胱的明显要大 .Kubelka Munk二流模型下 ,两种组织对同一波长的激光或其线偏振激光的光学特性均有显著性差异 (P <0 0 1) .同一组织对不同波长的激光及其线偏振激光的光学特性也有显著性差异 (P <0 0 1) ,正常膀胱组织对同一波长的激光及其线偏振激光的光学性有明显差异 ,而膀胱癌组织对同一波长的激光及其线偏振激光的光学特性则没有明显差异 .膀胱癌组织对 5 32nm和 80 8nm激光及其线偏振激光的前向散射通量i (x)、后向散射通量 j (x)、总散射通量I (x)的衰减均较正常膀胱组织的明显要大得多 ,且其i (x)均明显较j (x)要强     

Selective in vivo tumor localization of heptacarboxylic porphyrin isomer I in a bladder tumor model: a novel technique to modulate porphyrin localization

We were the first to report that uroporphyrin isomer I is a superior tumor localizer when compared with hematoporphyrin derivative. In the present study, we have examined the tumor localization of heptacarboxylic porphyrin isomer I (hepta-P) using a bladder tumor model. We have also compared it to that found with uroporphyrin isomer I (Uro-P). We now show, for the first time, that (hepta-P) isomer I can be selectively retained in bladder malignant cells, a novel observation which has not yet been described by other investigators. Furthermore, we have provided a novel technique to modulate and manipulate blood protein binding to porphyrin in a controlled manner, such that the tumor localization properties can be effectively utilized without prolonged retention in the skin and to produce high uptake in the tumor, i.e., a higher therapeutic ratio. The biodistribution of hepta-P in different organs is presented.     

Construction and application of urinary system model with functional bladder module

In order to study the construction and application of urinary system model with functional bladder module, bladder model was designed, and appropriate materials was selected to make it, and its performance was studied. The results showed that in the analysis of pressure performance of bladder model, more detrusor instability was found in the model than in the urodynamic test, and there was significant statistical difference (P < 0.01). In the analysis of bladder safety capacity, it was found that the bladder safety capacity in the model was much larger than that measured by urodynamics, and there was significant statistical difference (P < 0.01). In the analysis of detrusor workmanship and contraction rate, it was found that the normal model group was significantly smaller than the obstruction group, and there was significant statistical difference (P < 0.01). Comparing the detrusor contraction rate of the two groups, it was found that the normal group and the obstruction group had significant difference at t3, and there was no statistical difference between the other two groups. Therefore, through this study, it is found that the understanding of urinary system can be enhanced by building bladder model, and the basic operating skills of medical staff can be improved more easily by using bladder model, which achieves the expected results of the experiment. Although some shortcomings have been found in the course of the study, it still provides experimental reference for the clinical study of bladder in the future.     

Immunoexpression Analysis and Prognostic Value of BLCAP in Breast Cancer

Bladder Cancer Associated Protein (BLCAP, formerly Bc10), was identified by our laboratory as being down-regulated in bladder cancer with progression. BLCAP is ubiquitously expressed in different tissues, and several studies have found differential expression of BLCAP in various cancer types, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer patients within the Danish Center for Translational Breast Cancer Research (DCTB) prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient sample matched cohort, that immunostaining intensity for BLCAP was increased in tumors relative to normal tissue, in more than 45% of the cases examined, indicating that BLCAP may be of value as a marker for breast cancer. We also analyzed BLCAP expression and prognostic value using a set of tissue microarrays comprising an independent cohort of 2,197 breast cancer patients for which we had follow-up clinical information.     

Cell type specific expression of the apoptosis stimulating protein (ASPP-2) in human tissues

Apoptosis stimulating proteins of p53 (ASPP-l and ASPP-2) are a novel family of proteins that have been found to co-stimulate p53 activation of Bax (Bcl-2 associated protein X) inducing caspase-mediated apoptosis. Therefore, these proteins may play an important role in regulating apoptosis in normal and neoplastic cells. However, their cellular and tissue distribution has not been documented. The aim of this study was to determine the localization pattern of ASPP-2 in a variety of normal and malignant human tissues, including liver, lung, prostate, small intestine, kidney, ovary, bladder, cervix, breast, stomach, bowel, gallbladder, endometrium, pancreas, spleen and thyroid.The distribution and expression of ASPP-2 was assessed by immunohistochemistry in a range of formalin-fixed, paraffin embedded, benign and malignant human tissues, using a mouse monoclonal antibody against ASPP-2.The results showed a variable pattern of positivity of ASPP-2 within the tissues studied. ASPP-2 expression was localized in the cytoplasmic paranuclear granules in the epithelial cells of most of the organs we studied. The pattern of staining intensity of ASPP-2 correlated to the maturation state in benign tissue and to the differentiation state in the context of bladder cancer.This study indicates that ASPP-2 has a specific distribution pattern within tissues and cells in a way that appears to be related to differentiation. However, the patterns are neither simplistic nor straightforward and will require further investigation in order to appreciate fully their physiological/pathological significance.     

Early molecular-level changes in rat bladder wall tissue following spinal cord injury

Previously, we demonstrated using a rat model of spinal cord injury (SCI) that bladder wall tissue compliance significantly increased within the first 2 weeks following injury. In order to explore the potential molecular-level mechanisms of this event, the present study quantified molecules pertinent to bladder tissue remodeling and changes in mechanical properties. An initial gene array analysis followed by real-time qPCR revealed that the message levels for tropoelastin and lysyl oxidase were as high as 8-fold in SCI rats compared to normal. Furthermore, both the message and protein levels of TGF-beta1 and IGF-1, known stimulators of elastin synthesis, in SCI rat bladders were significantly higher compared to those of normal rats. Taken together, it can be speculated that functional changes of the bladder associated with SCI induce release of select growth factors, which, in turn, stimulate elastogenesis that lead to alteration of biomechanical properties of the wall tissue.     

Defects formation and spiral waves in a network of neurons in presence of electromagnetic induction

Complex anatomical and physiological structure of an excitable tissue (e.g., cardiac tissue) in the body can represent different electrical activities through normal or abnormal behavior. Abnormalities of the excitable tissue coming from different biological reasons can lead to formation of some defects. Such defects can cause some successive waves that may end up to some additional reorganizing beating behaviors like spiral waves or target waves. In this study, formation of defects and the resulting emitted waves in an excitable tissue are investigated. We have considered a square array network of neurons with nearest-neighbor connections to describe the excitable tissue. Fundamentally, electrophysiological properties of ion currents in the body are responsible for exhibition of electrical spatiotemporal patterns. More precisely, fluctuation of accumulated ions inside and outside of cell causes variable electrical and magnetic field. Considering undeniable mutual effects of electrical field and magnetic field, we have proposed the new Hindmarsh–Rose (HR) neuronal model for the local dynamics of each individual neuron in the network. In this new neuronal model, the influence of magnetic flow on membrane potential is defined. This improved model holds more bifurcation parameters. Moreover, the dynamical behavior of the tissue is investigated in different states of quiescent, spiking, bursting and even chaotic state. The resulting spatiotemporal patterns are represented and the time series of some sampled neurons are displayed, as well.