这项工作是由来自合作研究和培训经验计划（CREATE）和发现格兰特从加拿大自然科学和工程研究理事会（NSERC）资助。

作者什么都没有透露。

我们已经提出了一系列的数字图像处理和模式识别的复杂的技术，也被称为机器学习与CAD，对结构扭曲的间隔癌症病例前乳房X线照片检测。该方法是基于存在于乳腺摄影图像的定向纹理图案的分析。我们的方法，其中包括一些在我们的相关工作提出了更多的功能，能够在不到4帧/病人22检测乳腺癌的早期迹象15个月提前临床诊断时，平均，有80％的敏感性，58。 在一个潜在的临床应用，标记我们的程序的投资回报应被视为提示由放射科医生仔细检查乳房X线照片的相应区域。关于乳腺癌的存在与否的最终决定是由放射科医生，谁可能要求额外的成像程序或进行临床测试，以验证或确认由乳房X光检查和CAD提出怀疑。 虽然我们的方法已在本回顾性研究提供了令人振奋的结果，他们还没有准备好用于临床。该方法采用每幅最长约6分钟的戴尔Precision 490的PWS工作站四核英特尔至强处理器工作在3.0 GHz，有12 GB的RAM上，需要计算的要求，由计算机代码优化实现降低。结果是相当于或高于所报道的关于结构扭曲的研究与商用CAD系统18,59,60，与目前的工作是基于前乳房X线照片的区别略胜一筹。需要FP的数量可以减少到约1每名患者具有至少80％的相关联的灵敏度。 在我们的工作中存在的由使用的模型检测的结构扭曲的类型方面的限制。该方法需要是睾丸D与更大的数据集。在该方法中使用的参数，这些参数已经在目前的工作中已经凭经验确定，需要就在一个给定的数据集进行分析的乳房X线照片的特性进行优化。我们希望我们的程序，导致与直接数字乳房X光检查和乳房断层合成图像比那些与扫描屏 - 片图像，在目前的工作中取得更好的成绩。 结论我们的方法表明承诺在结构扭曲和乳腺癌在早期阶段检测。进一步的工作是必须实现结构扭曲的高灵敏度和低计划生育率的检测。

乳腺癌是影响妇女的一大疾病，是女性1,2癌症相关死亡的第二大原因。为了改善生存的机会和受影响的患者中，通过有效的治疗在乳腺癌的早期阶段的预后，疾病需要尽可能早地检测到。在乳腺癌病例的回顾性分析，异常微妙的迹象已发现在先前获得的乳房X光检查3,4。结构扭曲为乳腺癌的可能的早期阶段，这样的一个局部的乳房X线标志，难以检测5,6。关联的图案依稀描述为与没有明确的质量可见乳房的正常结构的畸变。结构扭曲可能出现在乳房肿块或肿瘤的形成的初始阶段。我们猜测，乳房X光检查前乳腺癌c中的检测获得乌尔德包含的乳腺癌的早期阶段细微的迹象，特别是建筑的失真。 图1a示出的屏幕检测癌症的情况下的现有的X线图像。异常确定由放射科医生（JELD）的区域中都列出了一个红色的矩形。在乳房X光检查前摄于图1b所示的检测乳房X光检查24个月前。在乳房X光检查之前已经被宣布为无癌症的迹象在筛选的原始实例。在回顾性分析，并与所述检测乳房X线照片，涉及到的检测到癌症部位可疑区域相比被标记由放射科医生，并以红色概述了现有乳房X线照片。可疑区域包含结构扭曲的迹象，包括骨针。 计算机辅助诊断（CAD）技术和系统提供的潜力，在Brea的实现检测的敏感性增加ST癌症2,7〜9。然而，在与存在于对乳腺癌的其他体征，如群众和钙化的检测文献的出版物的数量的比较，只有少量的研究已经报道了结构扭曲的检测中没有一个中央大规模10-17。商业上可用的CAD系统已经被发现在结构扭曲18的检测表现不佳。研究结构扭曲的屏幕检测或间隔癌症病例3,4,19-22可以帮助开发对乳腺疾病的检测和治疗策略在早期阶段，并导致改善的前乳房X线照片检测预后的病人23。 对于实验制备的图片实验用158 X线影像，包括56个人106前乳房X线照片进行诊断乳腺癌患者和13例正常个体52的图像。从交合卫生研究伦理委员会，医学伦理办公室，卡尔加里大学和卡尔加里地区卫生局获得伦理委员会批准为研究对象。这些图像是从屏幕测试获得:阿尔伯塔程序的早期检测乳腺癌21,24,25。 在过去的预定访问筛查方案的癌症筛查计划外的诊断之前收购的乳房X线照片被打成区间癌症病例的乳房X线照片前。相应的诊断乳房X光摄影是不允许的。除了两个106前乳房X线照片已被宣布为无患乳腺癌的迹象在他们的采集和分析的筛查方案的时候，对应的另外两个乳房X线照片的人已转交活检。癌症的诊断和前乳房X线照片之间的时间间隔范围从1.5个月s到24.5个月，平均15个月和7个月的标准偏差。所有区间的癌症病例数据库中可用的乳房X线照片前已经包含在本研究中，除了其中没有可疑的地方可确定六幅图像。 屏幕膜乳房X线照片进行数字化，在50微米和每像素12位使用Lumiscan 85激光扫描器（Lumisys，桑尼维尔，CA）的灰度分辨率的空间分辨率。专家放射科医生专门从事乳腺X线摄影（JELD）审阅所有间隔癌症病例106前乳房X线照片，并标明结构扭曲的可疑区域与矩形框的基础上对后续成像或活检可用的报告，或者通过乳房X线照片的详细检查。在106之前，X线影像在本研究中所使用的数据集，38图像有明显的结构扭曲，其余68图像包含可疑或不明确EVIDENT结构扭曲。每个乳房X光检查之前包含结构扭曲的一个站点所确定的矩形框由放射科医生得出。的平均宽度，高度，和标记的放射图像的106份可疑的区域56毫米，39毫米，和2274毫米2，用11.8毫米分别标准偏差为11.6毫米，并1073.9毫米2。

detection of architectural distortion in prior mammograms via analysis of oriented patterns

我们展示的结构扭曲的间隔癌症病例的基础上，乳腺组织模式在乳房X线照片的取向分析前乳房X线照片检测方法。我们推测，结构扭曲修改的乳腺组织模式在X线影像的正常方向群众或肿瘤形成之前。在我们的方法的初始步骤中，导向结构在给定的乳房X光检查正在使用的Gabor滤波器和相图分析，以检测辐射或交叉组织模式的节点类网站。然后每个检测到的网站的特点是使用节点值，分形维数和度量角色散的专门用来表示与结构扭曲相关spiculating模式。 我们的方法进行了测试用的56区间的癌症病例使用的开发功能106前乳房X线照片和52 13乳房X光检查正常情况下的数据库表征结构扭曲， 通过二次判别分析模式分类，并验证与留一病人出程序。根据自由反应受试者工作特征分析的结果，我们的方法已经证明，检测结构扭曲在乳房X线照片前的能力，在关于乳腺癌的临床诊断前服用15个月（平均），用80％的敏感性每名患者5误报。

这三个特点，即，节点值，FD和H 24 F，0.61提供AUC值，0.59和0.64时，分别各功能是用于自身。结合使用的三个特点提供更好的性能与AUC = 0.70。同的三个特征的组合中得到的FROC曲线示于图11，它表示80％的5.6帧/患者和89％的7.5帧/患者的敏感性。仅使用节点值在8.1帧/病人和89％，至13.8帧/病人提供了80％的敏感性。 FP的最终结果的减少被示于图12。为说明起见，只有6具有最高排名的ROI被显示。括号外的数字表示基于由贝叶斯分类中获得的判别式值的排名，括号内的数字对应于基于节点的地图上较早的排名。比较<s<html> TRONG&gt;图12与检测图7所示的可疑ROI的初始阶段，很显然，用于表征结构扭曲的功能，导致大量减少FP的，与节点分析的初始阶段相比，在保持检测的灵敏度良好。这是3的高度排列的ROI的已重叠标志着由放射科医师结构扭曲的可疑区域，并且通过我们的程序表示检测成功的情况下的情况。 在临床应用中，将要显示在最终结果中的ROI的数量应根据所需的灵敏度和FP的数目将是不能容忍的，以及在放射科医师的喜好来确定。 <html> oad/50341/50341fig1.jpg"/&gt; 图1。尺寸（A）乳房X光检查前1,377 850倍的像素为200微米/像素的分辨率;尺寸1374 850倍的像素为200微米/像素分辨率（一）相应的检测乳房X光检查，图像中的结构扭曲（三）放大显示区域在部分（A），尺寸39.2毫米x21.8毫米，在部分（B）所示的图像中结构扭曲的（D）放大区，大小40.8毫米x26.8毫米的大小。在乳房X光检查之前拍摄的乳房X光检测24个月前。这是筛查检出乳腺癌的情况。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig1highres.jpg" target="_blank">点击这里查看大图。</a> 41fig2highres.jpg"/&gt; 图2。在200微米/像素分辨率（A）之前的大小1377 850倍像素的乳房X光检查;预处理对乳房区域的近似分割后对应的图像（B） <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig2highres.jpg" target="_blank">点击此处查看大图。</a> <img alt="图3" width="500" src="/files/ftp_upload/50341/50341fig3.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig3highres.jpg" /> 图3。图像显示能量集中在几个角度（B）傅立叶幅度谱;（C）的Gabor幅度响应;和（D）的Gabor角度响应（A）测试工厂与几个导向件，尺寸646 x 668像素的图像。 180 Gabor滤波器中使用超过范围-90°〜+90°，Τ </em<html> &gt; = 8个像素，L = 8。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig3highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图4" width="500" src="/files/ftp_upload/50341/50341fig4highres.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig4highres.jpg" /> 图4。 （A）的Gabor幅值的大小1377 850倍像素，每个像素200微米，与图2B所示的结构扭曲的乳房X线照片（B）的角响应。 180 Gabor滤波器被用来在范围-90°至90°，Τ= 4个像素，L = 8。矩形（红色或绿色）显示标记的放射结构扭曲的面积，尺寸为47.6毫米×29.9毫米（C），（D）的放大视图结构扭曲的区域。es/ftp_upload/50341/50341fig4highres.jpg"目标="_blank"&gt;点击这里查看大图。 <img alt="图5" width="500" src="/files/ftp_upload/50341/50341fig5.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig5.jpg" /> 图5中的网管技术:细长的矩形（在灰色）表示CLS的存在。正方形表示像素沿垂直于CLS的取向方向。中央的绿色方块表示一个核心CLS像素。 <img alt="图6" width="500" src="/files/ftp_upload/50341/50341fig6.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig6highres.jpg" /> 图6。NMS和CLS评选结果叠加在图2A全乳腺图像上（A）网管结果（B）选择CLS结果。标志着白色对应于被保留作进一步的分析CLS像素的像素。（C）NMS结果和（D）CLS评选结果在放大视图标注在图4A的投资回报率。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig6highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图7" width="500" src="/files/ftp_upload/50341/50341fig7.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig7highres.jpg" /> 图7。 （一）节点图及（b）的ROI检测到在图2B所示的乳房X线照片。在乳腺摄影图像是大小为1377放大850倍的像素在每个像素200微米。结构扭曲的标记由放射科医师的区域（红色矩形）的大小47.6毫米×29.9毫米。每个感兴趣区域是尺寸为128×128像素，除了在即时通讯的边缘年龄。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig7highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图8" width="500" src="/files/ftp_upload/50341/50341fig8.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig8highres.jpg" /> 图8（A）的例子- （C）3 TP的ROI和（D） - （F）3 FP的投资回报。每个投资回报率的大小为128×128像素。显示对应的节点值。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig8highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图9" width="500" src="/files/ftp_upload/50341/50341fig9.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig9highres.jpg" /> 图9。 （A）128×128象素TP的投资回报率与建筑DIS<html>失真;像素尺寸= 200微米。节点值= 0.0299（B）的二维傅立叶数功率谱S应用冯Hann窗和补零的投资回报为256×256像素之后（U，V）获得的（C）在（F的功率谱， Ν）的空间。水平轴对应于角度Ν从0°到179°，而垂直轴对应于径向频率从0.02毫米-1至2.5mm -1。的左上角的像素对应于0.02毫米-1和0°角频率。黑色框架已应用于光谱（D）电源的角度扩展，S（Ν）。熵HF = 7.2224（E）的一维功率谱S（F）绘制在对数标度的径向频率 f的函数。的线性拟合也显示（红线），这导致FD = 2.3037为TP的ROI。ARGET ="_blank"&gt;点击这里查看大图。 <img alt="图10" width="500" src="/files/ftp_upload/50341/50341fig10.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig10highres.jpg" /> 图10。 （A）128×128像素的FP的投资回报率;像素大小为200微米。投资回报率造成的FP节点由于重叠和/或交叉的正常结构。节点值= 0.0349（B）的二维傅立叶数功率谱S应用冯Hann窗和补零的投资回报为256×256像素之后（U，V）获得的（C）在（F的功率谱， Ν）的空间。水平轴对应于角度Ν从0°到179°，而垂直轴对应于径向频率从0.02毫米-1至2.50毫米-1。的左上角的像素对应于0.02毫米-1和0°角频率。由BL<html> ACK帧已被应用到的光谱（D）功率的角度扩展，S（Ν）。熵HF = 6.9444（E）的一维功率谱S（F）绘制在对数标度的径向频率 f的函数。线性拟合也显示（红色线），导致FD = 2.5223对FP的投资回报率。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50341/50341fig10large.jpg" target="_blank">点击这里查看大图</a> 。 <img alt="图11" width="500" src="/files/ftp_upload/50341/50341fig11.jpg" fo:content-width="4.5in" fo:src="/files/ftp_upload/50341/50341fig11highres.jpg" /> 图11。FROC曲线示出了所提出的特性的检测性能。 oad/50341/50341fig12highres.jpg"/&gt; 图12。ROI的为图2中所示的原始乳房X线照片的最终标识。在处理的早期阶段检测到的可疑的ROI被显示在图7。用绿色标出的矩形表示TP的ROI分析中的最后阶段，在黄色中列出的剩余矩形表示fps或误报。红色矩形表示标志着由放射科医生对本研究结构扭曲的区域，在应用到本案的留一病人出过程中没有使用该信息并不会提供的一个应用前景提出的方法。

Watch this Scientific Journal Video about Detection of Architectural Distortion in Prior Mammograms via Analysis of Oriented Patterns at JoVE.com

Detection of Architectural Distortion in Prior Mammograms via Analysis of Oriented Patterns

我们展示的结构扭曲的前乳房X线照片检测方法。面向结构采用Gabor滤波器和相图来检测辐射组织模式的网站进行分析。每个网站的特点和分类使用的措施表示spiculating模式。该方法应有助于乳腺癌的检测。

在检测之前乳房X光检查建筑失真<em&gt;通过</em面向模式的&gt;分析

We demonstrate methods for the detection of architectural distortion in prior mammograms of interval-cancer cases based on analysis of the orientation of ...

detection-architectural-distortion-prior-mammograms-via-analysis

Nanyang Technological University

Research

JoVE Journal

Medicine

Detection of Architectural Distortion in Prior Mammograms via Analysis of Oriented Patterns

42.6K 次观看.  University of Calgary. 我们展示的结构扭曲的前乳房X线照片检测方法。面向结构采用Gabor滤波器和相图来检测辐射组织模式的网站进行分析。每个网站的特点和分类使用的措施表示spiculating模式。该方法应有助于乳腺癌的检测。 

视频: Detection of Architectural Distortion in Prior Mammograms via Analysis of Oriented Patterns

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities1-3. PET is characterized by its excellent sensitivity and quantification ability while OI is notable for non-radiation, relative low cost, short scanning time, high throughput, and wide availability to basic researchers. However, both modalities have their shortcomings as well. PET suffers from poor spatial resolution and high cost, while OI is mostly limited to preclinical applications because of its limited tissue penetration along with prominent scattering optical signals through the thickness of living tissues.
 Recently a bridge between PET and OI has emerged with the discovery of Cerenkov Luminescence Imaging (CLI)4-6. CLI is a new imaging modality that harnesses Cerenkov Radiation (CR) to image radionuclides with OI instruments. Russian Nobel laureate Alekseyevich Cerenkov and his colleagues originally discovered CR in 1934. It is a form of electromagnetic radiation emitted when a charged particle travels at a superluminal speed in a dielectric medium7,8. The charged particle, whether positron or electron, perturbs the electromagnetic field of the medium by displacing the electrons in its atoms. After passing of the disruption photons are emitted as the displaced electrons return to the ground state. For instance, one 18F decay was estimated to produce an average of 3 photons in water5. 
 Since its emergence, CLI has been investigated for its use in a variety of preclinical applications including in vivo tumor imaging, reporter gene imaging, radiotracer development, multimodality imaging, among others4,5,9,10,11. The most important reason why CLI has enjoyed much success so far is that this new technology takes advantage of the low cost and wide availability of OI to image radionuclides, which used to be imaged only by more expensive and less available nuclear imaging modalities such as PET.
 Here, we present the method of using CLI to monitor cancer drug therapy. Our group has recently investigated this new application and validated its feasibility by a proof-of-concept study12. We demonstrated that CLI and PET exhibited excellent correlations across different tumor xenografts and imaging probes. This is consistent with the overarching principle of CR that CLI essentially visualizes the same radionuclides as PET. We selected Bevacizumab (Avastin; Genentech/Roche) as our therapeutic agent because it is a well-known angiogenesis inhibitor13,14. Maturation of this technology in the near future can be envisioned to have a significant impact on preclinical drug development, screening, as well as therapy monitoring of patients receiving treatments.

Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring

Use of Cerenkov Luminescence Imaging (CLI) for monitoring preclinical cancer treatment is described here. This method takes advantage of Cerenkov Radiation (CR) and optical imaging (OI) to visualize radiolabeled probes and thus provides an alternative to PET in preclinical therapeutic monitoring and drug screening.

癌症治疗监测的切伦科夫发光成像（CLI）

In  molecular imaging, positron emission tomography (PET) and optical imaging (OI)  are two of the most important and thus most widely used modalities1-3. ...

科研

医学

Identification of Disease-related Spatial Covariance Patterns using Neuroimaging Data

The scaled subprofile model (SSM)1-4 is a multivariate PCA-based algorithm that identifies major sources of variation in patient and control group brain image data while rejecting lesser components (Figure 1). Applied directly to voxel-by-voxel covariance data of steady-state multimodality images, an entire group image set can be reduced to a few significant linearly independent covariance patterns and corresponding subject scores. Each pattern, termed a group invariant subprofile (GIS), is an orthogonal principal component that represents a spatially distributed network of functionally interrelated brain regions. Large global mean scalar effects that can obscure smaller network-specific contributions are removed by the inherent logarithmic conversion and mean centering of the data2,5,6. Subjects express each of these patterns to a variable degree represented by a simple scalar score that can correlate with independent clinical or psychometric descriptors7,8. Using logistic regression analysis of subject scores (i.e. pattern expression values), linear coefficients can be derived to combine multiple principal components into single disease-related spatial covariance patterns, i.e. composite networks with improved discrimination of patients from healthy control subjects5,6. Cross-validation within the derivation set can be performed using bootstrap resampling techniques9. Forward validation is easily confirmed by direct score evaluation of the derived patterns in prospective datasets10. Once validated, disease-related patterns can be used to score individual patients with respect to a fixed reference sample, often the set of healthy subjects that was used (with the disease group) in the original pattern derivation11. These standardized values can in turn be used to assist in differential diagnosis12,13 and to assess disease progression and treatment effects at the network level7,14-16. We present an example of the application of this methodology to FDG PET data of Parkinson's Disease patients and normal controls using our in-house software to derive a characteristic covariance pattern biomarker of disease.

Multivariate techniques including principal component analysis (PCA) have been used to identify signature patterns of regional change in functional brain images. We have developed an algorithm to identify reproducible network biomarkers for the diagnosis of neurodegenerative disorders, assessment of disease progression, and objective evaluation of treatment effects in patient populations.

鉴定的使用神经影像学数据的与疾病-相关的的空间协方差模式

The scaled subprofile model (SSM)1-4 is a multivariate PCA-based algorithm that identifies major sources of variation in patient and control group brain ...

Collecting Saliva and Measuring Salivary Cortisol and Alpha-amylase in Frail Community Residing Older Adults via Family Caregivers

Salivary measures have emerged in bio-behavioral research that are easy-to-collect, minimally invasive, and relatively inexpensive biologic markers of stress. This article we present the steps for collection and analysis of two salivary assays in research with frail, community residing older adults-salivary cortisol and salivary alpha amylase. The field of salivary bioscience is rapidly advancing and the purpose of this presentation is to provide an update on the developments for investigators interested in integrating these measures into research on aging. Strategies are presented for instructing family caregivers in collecting saliva in the home, and for conducting laboratory analyses of salivary analytes that have demonstrated feasibility, high compliance, and yield quality specimens. The protocol for sample collection includes: (1) consistent use of collection materials; (2) standardized methods that promote adherence and minimize subject burden; and (3) procedures for controlling certain confounding agents. We also provide strategies for laboratory analyses include: (1) saliva handling and processing; (2) salivary cortisol and salivary alpha amylase assay procedures; and (3) analytic considerations.

We demonstrate: (1) procedures for collection of salivary samples in cognitive impaired older adults by family caregivers in the home setting, (2) procedures for measuring stress activity via salivary cortisol and alpha amylase, and (3) representative profiles. Protocols that allow researchers to study stress-linked processes advance our understanding of biological sensitivity and susceptibility.

Salivary measures have emerged in bio-behavioral research  that are easy-to-collect, minimally invasive, and relatively inexpensive  biologic markers of ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

颈动脉输液的紫杉烷类化合物在小鼠体内的药代动力学和药效学分析

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

跟踪乳腺建筑特色与检测乳腺癌的磁共振扩散张量成像

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods.
Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes.
In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated.

Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

The severe organ shortage has resulted in increased use of marginal kidney grafts for transplantation. This has triggered interest in alternative storage methods, since marginal grafts especially tolerate cold storage poorly. The technique of normothermic ex vivo kidney perfusion (NEVKP) represents a novel preservation method for kidney grafts prior to &#160;transplantation.

常温<em&gt;离体</em&gt;肾脏的灌注肾的移植保护移植前

Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a ...

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma

Understanding tumor clonality is critical to understanding the mechanisms involved in tumorigenesis and disease progression. In addition, understanding the clonal composition changes that occur within a tumor in response to certain micro-environment or treatments may lead to the design of more sophisticated and effective approaches to eradicate tumor cells. However, tracking tumor clonal sub-populations has been challenging due to the lack of distinguishable markers. To address this problem, a VDJ-seq protocol was created to trace the clonal evolution patterns of diffuse large B cell lymphoma (DLBCL) relapse by exploiting VDJ recombination and somatic hypermutation (SHM), two unique features of B cell lymphomas.
In this protocol, Next-Generation sequencing (NGS) libraries with indexing potential were constructed from amplified rearranged immunoglobulin heavy chain (IgH) VDJ region from pairs of primary diagnosis and relapse DLBCL samples. On average more than half million VDJ sequences per sample were obtained after sequencing, which contain both VDJ rearrangement and SHM information. In addition, customized bioinformatics pipelines were developed to fully utilize sequence information for the characterization of IgH-VDJ repertoire within these samples. Furthermore, the pipeline allows the reconstruction and comparison of the clonal architecture of individual tumors, which enables the examination of the clonal heterogeneity within the diagnosis tumors and deduction of clonal evolution patterns between diagnosis and relapse tumor pairs. When applying this analysis to several diagnosis-relapse pairs, we uncovered key evidence that multiple distinctive tumor evolutionary patterns could lead to DLBCL relapse. Additionally, this approach can be expanded into other clinical aspects, such as identification of minimal residual disease, monitoring relapse progress and treatment response, and investigation of immune repertoires in non-lymphoma contexts.

This protocol describes an approach to interrogate the recombined immunoglobulin heavy chain VDJ regions of lymphomas by deep-sequencing and retrieve VDJ rearrangement and somatic hypermutation status to delineate clonal architecture of individual tumor. Comparing clonal architecture between paired diagnosis and relapse samples reveals lymphoma relapse clonal evolution modes.

VDJ-SEQ:重排免疫球蛋白重链基因的深度测序分析，以揭示的B细胞淋巴瘤克隆演变模式

Understanding tumor clonality is critical to understanding the mechanisms involved in tumorigenesis and disease progression. In addition, understanding ...

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic patient tumors in different assays1. Human tumor xenografts represent the gold standard with respect to tumor biology, drug discovery, and metastasis research 2-4. Tumor xenografts can be derived from different types of material like tumor cell lines, tumor tissue from primary patient tumors4 or serially transplanted tumors. When propagated in vivo, xenografted tissue is infiltrated and vascularized by cells of mouse origin. Multiple factors such as the tumor entity, the origin of xenografted material, growth rate and region of transplantation influence the composition and the amount of mouse cells present in tumor xenografts. However, even when these factors are kept constant, the degree of mouse cell contamination is highly variable.
Contaminating mouse cells significantly impair downstream analyses of human tumor xenografts. As mouse fibroblasts show high plating efficacies and proliferation rates, they tend to overgrow cultures of human tumor cells, especially slowly proliferating subpopulations. Mouse cell derived DNA, mRNA, and protein components can bias downstream gene expression analysis, next-generation sequencing, as well as proteome analysis 5. To overcome these limitations, we have developed a fast and easy method to isolate untouched human tumor cells from xenografted tumor tissue. This procedure is based on the comprehensive depletion of cells of mouse origin by combining automated tissue dissociation with the benchtop tissue dissociator and magnetic cell sorting. Here, we demonstrate that human target cells can be can be obtained with purities higher than 96% within less than 20 min independent of the tumor type.

Human tumor xenografts are vascularized and infiltrated by cells of mouse origin during the growth phase in vivo. To circumvent the bias caused by these contaminating cells during downstream analysis, we developed a method allowing for comprehensive depletion of all mouse cells by magnetic cell sorting.

从人类肿瘤异种移植的小鼠细胞的消耗显着改善靶细胞下游分析

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic ...

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Here, a protocol involving re-arterialized rat partial liver transplantation is presented. Specifically, 70% liver was resected in vivo by using an updated technique of vessel-oriented hepatectomy. The hepatic artery was reconstructed in an end-to-side manner. The cuff technique was modified to shorten the anastomosis time of the infrahepatic vena cava.

静脉大鼠部分肝移植的体内血管定向70% 肝切除术

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

High-Throughput Analysis of Optical Mapping Data Using ElectroMap

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we present, in a step-by-step guide, the use of ElectroMap for analysis, quantification, and mapping of high-resolution voltage and calcium datasets acquired by optical mapping. ElectroMap analysis options cover a wide variety of key electrophysiological parameters, and the graphical user interface allows straightforward modification of pre-processing and parameter definitions, making ElectroMap applicable to a wide range of experimental models. We show how built-in pacing frequency detection and signal segmentation allows high-throughput analysis of entire experimental recordings, acute responses, and single beat-to-beat variability. Additionally, ElectroMap incorporates automated multi-beat averaging to improve signal quality of noisy datasets, and here we demonstrate how this feature can help elucidate electrophysiological changes that might otherwise go undetected when using single beat analysis. Custom modules are included within the software for detailed investigation of conduction, single file analysis, and alternans, as demonstrated here. This software platform can be used to enable and accelerate the processing, analysis, and mapping of complex cardiac electrophysiology.

This protocol describes the setup and use of ElectroMap, a MATLAB-based open-source software platform for analysis of cardiac optical mapping data. ElectroMap provides a versatile high-throughput tool for analysis of optical mapping voltage and calcium datasets across a wide range of cardiac experimental models.

使用电子地图的光映射数据的高通量分析

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we ...