RESUMO
Angiogenesis is a key step in the initiation and progression of an invasive breast cancer. High microvessel density by morphological characterization predicts metastasis and poor survival in women with invasive breast cancers. However, morphologic characterization is subject to variability and only can evaluate a limited portion of an invasive breast cancer. Consequently, breast Magnetic Resonance Imaging (MRI) is currently being evaluated to assess vascularity. Recently, through the new field of radiomics, dynamic contrast enhanced (DCE)-MRI is being used to evaluate vascular density, vascular morphology, and detection of aggressive breast cancer biology. While DCE-MRI is a highly sensitive tool, there are specific features that limit computational evaluation of blood vessels. These include (1) DCE-MRI evaluates gadolinium contrast and does not directly evaluate biology, (2) the resolution of DCE-MRI is insufficient for imaging small blood vessels, and (3) DCE-MRI images are very difficult to co-register. Here we review computational approaches for detection and analysis of blood vessels in DCE-MRI images and present some of the strategies we have developed for co-registry of DCE-MRI images and early detection of vascularization.
RESUMO
Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Breast cancers that rapidly develop between breast image screening are called "interval cancers." The efforts of our team focus on identifying multiscale integrated strategies to identify biologically aggressive precancerous breast lesions. Our goal is to identify spatiotemporal changes that occur prior to development of interval breast cancers. To accomplish this requires integration of new technology. Our team has the ability to perform single cell in situ transcriptional profiling, noncontrast biological imaging, mathematical analysis, and nanoscale evaluation of receptor organization and signaling. These technological innovations allow us to start to identify multidimensional spatial and temporal relationships that drive the transition from biologically aggressive precancer to biologically aggressive interval breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics.
Assuntos
Neoplasias da Mama , Lesões Pré-Cancerosas , Biologia , Biópsia , Neoplasias da Mama/genética , Feminino , Humanos , Mamografia , Lesões Pré-Cancerosas/genéticaRESUMO
Cancer biomarker research has become a data-intensive discipline requiring innovative approaches for data analysis that can combine traditional and data-driven methods. Significant leveraging can be done transferring methodologies and capabilities across scientific disciplines, such as planetary science and astronomy, each of which are grappling with and developing similar solutions for the analysis of massive scientific data.
Assuntos
Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Neoplasias/metabolismo , Astronomia , Big Data , Humanos , Comunicação Interdisciplinar , National Institutes of Health (U.S.) , Medicina de Precisão , Estados Unidos , United States National Aeronautics and Space AdministrationRESUMO
BACKGROUND: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls. RESULTS: Three pure total human RNA samples (brain, liver, and placenta) and two different mixtures of these components were evaluated as measurement assurance control samples on multiple measurement systems at multiple sites and over multiple rounds. In silico modeling of mixtures provided benchmark values for comparison with physical mixtures. Biomarker development laboratories using next-generation sequencing (NGS) or genome-scale hybridization assays participated in the study and returned data from the samples using their routine workflows. Multiplexed and single assay reverse-transcription PCR (RT-PCR) was used to confirm in silico predicted sample differences. Data visualizations and summary metrics for genome-scale miRNA profiling assessment were developed using this dataset, and a range of performance was observed. These metrics have been incorporated into an online data analysis pipeline and provide a convenient dashboard view of results from experiments following the described design. The website also serves as a repository for the accumulation of performance values providing new participants in the project an opportunity to learn what may be achievable with similar measurement processes. CONCLUSIONS: The set of reference samples used in this study provides benchmark values suitable for assessing genome-scale miRNA profiling processes. Incorporation of these metrics into an online resource allows laboratories to periodically evaluate their performance and assess any changes introduced into their measurement process.