Quantitative Microscopy in Medicine

Alexandre Matov
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Abstract

Methods for personalizing medical treatment are the focal point of contemporary biomedical research. In cancer care, we can analyze the effects of therapies at the level of individual cells. Quantitative characterization of treatment efficacy and evaluation of why some individuals respond to specific regimens, whereas others do not, requires additional approaches to genetic sequencing at single time points. Methods for the analysis of changes in phenotype, such as in vivo and ex vivo morphology and localization of cellular proteins and organelles can provide important insights into patient treatment options. Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface glycoprotein that is commonly overexpressed by prostate cancer (PC) cells relative to normal prostate cells, provides a validated target. We developed a software for image analysis designed to identify PSMA expression on the surface of epithelial cells in order to extract prognostic metrics. In addition, our software can deliver predictive information and inform clinicians regarding the efficacy of PC therapy. We can envisage additional applications of our software system, beyond PC, as PSMA is expressed in a variety of tissues. Our method is based on image denoising, topologic partitioning, and edge detection. These three steps allow to segment the area of each PSMA spot in an image of a coverslip with epithelial cells. Our objective has been to present the community with an integrated, easy to use by all, tool for resolving the complex cytoskeletal organization and it is our goal to have such software system approved for use in the clinical practice.
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医学定量显微镜
个性化医疗方法是当代生物医学研究的焦点。在癌症治疗中,我们可以从单个细胞层面分析治疗效果。要定量分析治疗效果,评估为什么有些人对特定的治疗方案有反应,而另一些人则没有,这就需要在单个时间点进行基因测序的基础上采取更多的方法。分析表型变化的方法,如体内和体外形态学以及细胞蛋白质和细胞器的定位,可以为患者的治疗方案提供重要的见解。延长转移性耐受性前列腺癌(mCRPC)患者的生存期需要新的疗法。前列腺特异性膜抗原(PSMA)是一种细胞表面糖蛋白,与正常前列腺细胞相比,前列腺癌(PC)细胞通常过度表达这种糖蛋白。我们开发了一款图像分析软件,旨在识别上皮细胞表面的 PSMA 表达,从而提取预后指标。此外,我们的软件还能提供预测信息,让临床医生了解 PC 治疗的疗效。我们可以设想我们的软件系统在 PC 以外的其他应用,因为 PSMA 在多种组织中都有表达。我们的方法基于图像去噪、拓扑分割和边缘检测。通过这三个步骤,就能在带有上皮细胞的盖玻片图像中分割出每个 PSMA 点的区域。我们的目标是向社会提供一种易于使用的综合工具,用于解析复杂的细胞骨架组织,我们的目标是让这种软件系统获得批准,用于临床实践。
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