Examining brain microstructure using structure tensor analysis of histological sections

The mammalian central nervous system has a tremendous structural complexity, and diffusion tensor imaging (DTI) is unique in its ability to extract microstructural tissue properties at a macroscopic scale. However, despite its widespread use and applications in clinical and research settings, accurate validation of DTI has notoriously lagged the advances in image acquisition and analysis. In this report, we demonstrate an approach to visualize and quantify the microscopic features of histological sections on multiple length scales using techniques derived from image texture analysis. Structure tensor (ST) analysis was applied to fluorescence microscopy images of rat brain sections to visualize and quantify tissue microstructure. Images were digitally color-coded based on the local orientation in the pixelwise ST implementation, which allowed direct visualization of white matter complexity at the microscopic level. A piecewise ST algorithm was also employed to quantify anisotropy and orientation at a resolution comparable to that typically acquired with DTI. Anisotropy measured with ST analysis of stained histological sections was highly correlated with anisotropy measured by ex vivo DTI of the same brains (R(2)=0.92). Furthermore, angular histograms, or Fiber Orientation Distributions (FODs), were computed to mimic similar measures derived from high angular resolution diffusion imaging methods. The FODs for each pixel were fit to a mixture of von Mises distributions to identify putative regions of multiple fiber populations (i.e. crossing fibers). Despite its current application to two-dimensional microscopy, the ST analysis is a novel approach to visualize and quantify microstructure in the central nervous system in both health and disease, and advances the available set of tools for validating DTI and other diffusion MRI techniques.     

游离与总前列腺特异抗原比值检测前列腺癌的临床应用

目的：探讨游离前列腺特异性抗原（F－PSA）与总前列腺特异性抗原（T－PSA）比值在鉴别前列腺增生（BPH）和前列腺癌（PCa)中的临床价值。方法：采用放射免疫分析法,同时检测175例良、恶性前列腺疾病患者血清T－PSA和F－PSA,并计算F－PSA／T－PSA。结果：T－PSA,F－PSA,PFSA／T－PSA检测PCa的敏感性分别为91．2％,80．8％,88．2％,特异性分别为55．1％,59．8％,87．9％,T－PSA在4－10ng/ml范围内,BPH组和PCa组F－PSA／T－PSA有极显著性差异（P＜0．01）,而T－PSA差异无显著意义（P＞0．05）。结论F－PSA／T－PSA比值检测PCa在保持敏感性的同时,可显著地提高其特异性,是筛选诊断早期PCa极有价值的指标。     

Tree crown detection and delineation in satellite images using probabilistic voting

Crop yield forecasting in a region has become an important research area due to global warming and related climate changes. Although this can be performed by available statistical information, obtaining recent and up to date data to extract reliable statistical information is not easy. Very high resolution satellite images can be used for this purpose. However, manually processing these images acquired from large regions is neither feasible nor reliable. Therefore, automated methods are needed for this purpose. In this study, we propose a novel method to help forecasting the crop yield in an orchard. The number of trees in an orchard with the size and type of each tree crown gives an approximate crop that can be harvested. Therefore, we focus on both tree crown detection and delineation for this purpose. The proposed method for tree crown detection is based on probabilistic voting. For tree crown delineation, we propose a watershed segmentation based ellipse fitting method. We tested the proposed method on 17 satellite images containing 13,476 trees. We compared the method with the classical local maxima/minima filtering and a recent method in literature using three more test images. These tests indicate the strengths and weaknesses of the proposed method.     

Clinical efficacy of prostate cancer detection using power doppler imaging in American and Japanese men

PURPOSE: The aim of this study was to compare the detection rates of tumor vascular flow as measured by power Doppler imaging (PDI) in 2 populations and to determine whether PDI can reduce the number of unnecessary prostate biopsies in men with serum prostate-specific antigen (PSA) concentrations less than 10.1 ng/ml. METHODS: The patient populations were Japanese (group 1) and American (group 2) men with either serum PSA concentrations of 4.1-10.0 ng/ml or abnormal findings on digital rectal examination (DRE) plus PSA concentrations less than 4.1 ng/ml. We compared the overall diagnostic accuracy of DRE, gray-scale transrectal sonography (TRUS), and PDI between the 2 groups. RESULTS: In total, 275 men were studied, 154 in group 1 and 121 in group 2. Cancer was identified in 27% of men in group 1 and in 60% of group 2. Men with cancer in both groups differed significantly in age, peripheral zone volume, and mean number of positive biopsy cores. The sensitivity and specificity of PDI in group 2 were significantly inferior to those in group 1. The negative predictive value (NPV) of PDI was significantly higher for group 1 than for group 2. The NPV of PDI in group 1 was equivalent to that for the combination of DRE and TRUS, whereas the NPV for PDI in group 2 was significantly inferior to that of DRE and TRUS.CONCLUSIONS: Tumor vascularity could be detected by PDI more effectively in Japanese men with cancer than in American men with cancer. We hypothesize that this difference was a result of larger cancer volumes and smaller prostates in the Japanese men. PDI did not provide any performance advantage over DRE and TRUS in avoiding unnecessary biopsies.     

Advances in ultrasound for the detection of prostate cancer

The introduction of ultrasound (US) microbubble contrast agents has dramatically expanded the possibilities for US detection of prostate cancer. Recent advances in US technology have increased the value of US contrast agents. Many newer US techniques, which are quite sensitive for detection of microbubbles, are yet to be explored for prostate applications. A critical evaluation of the current status of transrectal US imaging for the detection of prostate cancer and background information for US contrast agents and imaging techniques are presented. Early results have demonstrated the feasibility of US contrast agents to enhance US imaging of prostatic disease. The application of US contrast agents for the detection and clinical staging of prostate cancer is promising. Future clinical trials are needed to determine whether the promise of contrast-enhanced US of the prostate will evolve into widespread clinical application.     

超声引导经直肠前列腺穿刺活检个体化方案的探讨

目的探讨个体化前列腺直肠径路穿刺活检方案的可行性。方法回顾性分析325例疑为前列腺癌患者首次穿刺的临床资料。采用系统12针组合穿刺方案,对可疑病变处补充1～2针,根据穿刺结果,分析穿刺阳性率与针数、体积的关系。结果126例患者确诊为前列腺癌。6、8、10针最大阳性率分别与12针穿刺阳性率比较,差异均有统计学意义。3个不同体积组比较,体积〈40ml组8针与10针阳性率差异无统计学意义,而40.1～60ml组8针与10针,〉60ml组10针与12针阳性率差异均有统计学意义。结论根据前列腺体积和超声表现制定个体化穿刺方案是可行的,体积〈40ml前列腺采用8针,40.1～60ml采用10针和〉60ml采用12针穿刺是合适的。     

Progensa PCA3 test for prostate cancer detection

Patients with an elevated serum total prostate-specific antigen value or abnormal digital rectal examination results are at risk of having prostate cancer and should undergo prostate needle biopsies. However, approximately 60% of them will have a negative prostate biopsy result. Therefore, further biopsies are recommended for young patients at risk of prostate cancer with a positive rate of 20-40%. Biomarkers are required in order to avoid unnecessary biopsies. The PCA3 gene product is specifically overexpressed in prostate tumor cells, and modern molecular biology techniques allow us to use a specific test for this gene in order to select patients who have a high risk of having prostate cancer. Literature reviews of the gene product, as well as the first clinical results of the Progensa PCA3 test, are presented.     

Restriction spectrum imaging improves MRI-based prostate cancer detection

Purpose

To compare the diagnostic performance of restriction spectrum imaging (RSI), with that of conventional multi-parametric (MP) magnetic resonance imaging (MRI) for prostate cancer (PCa) detection in a blinded reader-based format.

Methods

Three readers independently evaluated 100 patients (67 with proven PCa) who underwent MP-MRI and RSI within 6 months of systematic biopsy (N = 67; 23 with targeting performed) or prostatectomy (N = 33). Imaging was performed at 3 Tesla using a phased-array coil. Readers used a five-point scale estimating the likelihood of PCa present in each prostate sextant. Evaluation was performed in two separate sessions, first using conventional MP-MRI alone then immediately with MP-MRI and RSI in the same session. Four weeks later, another scoring session used RSI and T2-weighted imaging (T2WI) without conventional diffusion-weighted or dynamic contrast-enhanced imaging. Reader interpretations were then compared to prostatectomy data or biopsy results. Receiver operating characteristic curves were performed, with area under the curve (AUC) used to compare across groups.

Results

MP-MRI with RSI achieved higher AUCs compared to MP-MRI alone for identifying high-grade (Gleason score greater than or equal to 4 + 3=7) PCa (0.78 vs. 0.70 at the sextant level; P < 0.001 and 0.85 vs. 0.79 at the hemigland level; P = 0.04). RSI and T2WI alone achieved AUCs similar to MP-MRI for high-grade PCa (0.71 vs. 0.70 at the sextant level). With hemigland analysis, high-grade disease results were similar when comparing RSI + T2WI with MP-MRI, although with greater AUCs compared to the sextant analysis (0.80 vs. 0.79).

Conclusion

Including RSI with MP-MRI improves PCa detection compared to MP-MRI alone, and RSI with T2WI achieves similar PCa detection as MP-MRI.

     

Automatic inference of articulated spine models in CT images using high-order Markov Random Fields

In this paper, we introduce a novel and efficient approach for inferring articulated 3D spine models from operative images. The problem is formulated as a Markov Random Field which has the ability to encode global structural dependencies to align CT volume images. A personalized geometrical model is first reconstructed from preoperative images before surgery, and subsequently decomposed as a series of intervertebral transformations based on rotation and translation parameters. The shape transformation between the standing and lying poses is achieved by optimizing the deformations applied to the intervertebral transformations. Singleton and pairwise potentials measure the support from the data and geometrical dependencies between neighboring vertebrae respectively, while higher-order cliques (groups of vertebrae) are introduced to integrate consistency in regional curves. Local vertebra modifications are achieved through a constrained mesh relaxation technique. Optimization of model parameters in a multimodal context is achieved using efficient linear programming and duality. Experimental and clinical evaluation of the vertebra model alignment obtained from the proposed method gave promising results. Quantitative comparison to expert identification yields an accuracy of 1.8±0.7mm based on the localization of surgical landmarks.     

Bone remodeling markers in the detection of bone metastases in prostate cancer

BACKGROUND: Early detection of bone metastases in prostatic carcinoma is very useful in treatment and prognosis of the disease. The aim of this work was to evaluate the sensitivity and specificity of a group of bone markers in order to discriminate between prostate carcinoma patients without (M(0)) and with (M(1)) bone metastases. METHODS: Sixty-seven non-treated patients with: benign prostate hyperplasia (n=21), prostatic carcinoma in several stages without bone metastases (T(X)M(0)) (n=31) and with bone metastases (T(X)M(1)) (n=15) were studied. The following markers were studied: (A) bone formation: (1) serum bone alkaline phosphatase, IRMA (Tandem Ostase, Beckman); (2) serum procollagen I amino-terminal propeptide (PINP), RIA (Orion Diagnostica); (B) bone resorption: (1) urinary collagen I amino-terminal telopeptide (NTX), ELISA (Ostex); (2) collagen I carboxy terminal telopeptide (CTX): (2A) urinary alpha-CTX, RIA (Osteometer), (2B) serum beta-CTX, Elecsys (Roche); (3) collagen I cross-linked carboxy terminal telopeptide (ICTP), RIA (Orion Diagnostica). RESULTS: Levels of all bone markers were significantly higher in group M(1) than in group M(0). A complete separation of groups M(0) and M(1) was achieved with PINP and beta-CTX (100% sensitivity and specificity). CONCLUSIONS: These results support the use of PINP or beta-CTX as a tool to confirm the presence or absence of bone metastases in the first staging of prostatic carcinoma patients.     

磁共振波谱成像在前列腺癌中的应用

前列腺癌在男性已成为第二个最常见的被诊断的癌症。前列腺癌的早期检测对该病的治疗尤为重要。有许多方法来检测前列腺癌。MR波谱成像(MRS)可较好地早期检测前列腺癌。作者将讨论MRS的原理,前列腺癌的不同诊断前方法,以及目前已应用于临床的不同的机器和设备。     

前列腺癌组织中PCNA、MVD表达与彩超血流检测的研究

目的：探讨前列腺癌组织中PCNA、MVD表达与彩超血流检测及临床病理关系。方法：对27例前列腺癌，29例前列腺增生症进行彩色多普勒超声（CDFI）检测，将前列腺内动脉血流显示情况进行分级，计测阻力指数（RI）；采用免疫组化（SP）法检测相对应标本内增殖细胞核抗原（PCNA）、微血管密度（MVD）的表达。结果：在前列腺癌中，PCNA、MVD表达强度与血流分级和病理分化有良好相关性，随血流分级增大和病理分化程度减低呈上升趋势, 转移癌RI、PCNA、MVD高于无转移者。前列腺增生症中PCNA、MVD表达强度、血流分级、RI均明显低于前列腺癌组织，两组各项指标间有显著性差异（P＜0.05）。结论：前列腺癌组织中PCNA、MVD表达与血流检测，可从不同角度反映前列腺癌血管生成情况，为临床诊治和预后评估提供信息。     

SVM for prostate cancer using electrical impedance measurements

Biopsies are currently the 'gold standard' method for identifying cancer of the prostate. While biopsies yield very accurate information regarding the area they sample, they are performed at discrete points and provide no information on the adjacent tissue. To enhance procedural accuracy, biopsies of a large number of sites are routinely carried out. Although more accurate, this method is both more complex and nevertheless remains discrete. In this paper, we evaluate the advantages of using bio-impedance information as the input for a support vector machines (SVMs) classifier to overcome these limitations. In this method, the biopsy probes are used as electrodes to obtain electrical impedance data during each biopsy sample. Using a computer model of the prostate, a SVM was trained and tested. Different tumor shapes and conductivity values, and the classifier's ability to generalize to these different properties, were examined. We demonstrate that by using this classifier the number of biopsies can be reduced and valuable information concerning the adjacent tissue which was not biopsied can be generated.     

Treatment of androgen-independent hormone refractory prostate cancer using docetaxel

Although prostate cancer patients with metastatic lesion initially respond to androgen ablation therapy, almost patients develop to hormone-refractory states. The optimal treatment for men with hormone refractory prostate cancer (HRPC) has not been established. Docetaxel is a semisynthetic taxane that inhibit tumor growth by induction of microtubule stabilization and promotion of bcl-2 inactivation, which induce apoptosis. Docetaxel as single agent has significant anti-tumor effect in HRPC patients. Docetaxel combined with estramustine or other antimicrotubular agents have shown further significant cytotoxicity in HRPC patients. In the United States, Food and Drug Administration (FDA) approved docetaxel, injection in combination with prednisone for the treatment of patients with advanced metastatic prostate cancer in 2004.     

彩色多普勒超声对血清前列腺特异性抗原轻度升高前列腺癌患者的检测价值

目的探讨经直肠彩色多普勒超声在血清前列腺特异性抗原(PSA)轻度升高的早期前列腺癌病灶的检测价值。方法对88例PSA为4.0~20.0ng/ml的患者,穿刺活检术前行经直肠多普勒超声检查,利用彩色直方图软件测定并评价前列腺双侧周缘区血流信号丰富程度,其结果与穿刺活检病理结果比较。利用受试者作业特征曲线(ROC)分析PSA、PSA密度(PSAD)及彩色多普勒超声对周缘区前列腺癌诊断的敏感性、特异性及曲线下面积。结果88例患者经穿刺病理诊断为前列腺癌30例(34.1%),前列腺增生39例(44.3%),前列腺增生伴慢性间质炎症19例(21.6%)。周缘区前列腺癌的彩色血流信号明显高于前列腺增生及前列腺炎症(P=0.0136),ROC曲线分析显示彩色多普勒超声在检测周缘区前列腺癌中的作用优于PSA但不如PSAD,三者曲线下面积分别为0.629,0.542和0.758。经直肠彩色多普勒超声对前列腺癌诊断的敏感性和特异性分别为47.5%和76.5%,PSAD对前列腺癌病灶检测的敏感性和特异性分别为92.3%和24.4%,经直肠彩色多普勒与PSAD相结合在检测周缘区前列腺癌的敏感性和特异性分别为100.0%和80.1%。结论经直肠彩色多普勒超声对提高PSA轻度升高人群中的前列腺癌病灶检出率有一定价值。     

Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models

We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway.     

Examination of cancer in mouse models using high-frequency quantitative ultrasound

Two mouse models of mammary cancer (a carcinoma and sarcoma) were examined using quantitative ultrasound (QUS). Scatterer property estimates, i.e., the average scatterer diameter (ASD) and average acoustic concentration (AAC), were estimated from regions-of-interest (ROIs) inside the tumors. Initially, the spherical Gaussian model was used over an analysis bandwidth of 10 to 25 MHz to obtain ASD and AAC estimates. ASD estimates were 31.7 +/- 9.36 microm and 31.0 +/- 7.20 microm for the carcinomas and sarcomas, respectively. AAC estimates were 6.77 +/- 8.75 dB[mm(-3)] and 9.87 +/- 9.24 dB[mm(-3)], respectively. The initial ASD and AAC estimates did not yield statistically significant differences between the two kinds of tumors (p = 0.83, 0.86 for the ASD and AAC estimates, respectively). However, optical photomicrographs revealed distinct morphologic differences between the tumors. F-tests on the average power spectra from the tumors revealed statistically significant differences between the spectra over the range of 16 to 25 MHz. ASD and AAC estimates using the spherical Gaussian model were then obtained over the new analysis bandwidth of 16 to 25 MHz. The new ASD estimates were 42.1 +/- 4.01 microm and 32.1 +/- 3.81 microm for the carcinomas and sarcomas, respectively. The new AAC estimates were 16.4 +/- 17.1 dB[mm(-3)] and 36.4 +/- 11.9 dB[mm(-3)], respectively. Statistically significant differences were observed for both the ASD and AAC estimates when using the new analysis bandwidth. Structural differences between the tumors were revealed by both QUS and optical photomicrographs.