Automated image analysis in histopathology: a valuable tool in medical diagnostics.
ABSTRACT Virtual pathology, the process of assessing digital images of histological slides, is gaining momentum in today's laboratory environment. Indeed, digital image acquisition systems are becoming commonplace, and associated image analysis solutions are viewed by most as the next critical step in automated histological analysis. Here, we document the advances in the technology, with reference to past and current techniques in histological assessment. In addition, the demand for these technologies is analyzed with major players profiled. As there are several image analysis software programs focusing on the quantification of immunohistochemical staining, particular attention is paid to this application in this review. Oncology has been a primary target area for these approaches, with example studies in this therapeutic area being covered here. Toxicology-based image analysis solutions are also profiled as these are steadily increasing in popularity, especially within the pharmaceutical industry. Reinforced by the phenomenal growth of the virtual pathology field, it is envisioned that the market for automated image analysis tools will greatly expand over the next 10 years.
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ABSTRACT: Virtual histology, the process of assessing digital images of histological slides, is gaining momentum in modern histopathology and digital image acquisition systems are becoming commonplace. Associated image processing and analysis methods can potentially complement traditional histological assessment methodologies.Aquaculture 03/2015; 442. DOI:10.1016/j.aquaculture.2015.02.034 · 1.83 Impact Factor
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ABSTRACT: Drug efficacy strongly depends on the presence of the drug substance at the target site. As vascularization is an important factor for the distribution of drugs in tissues, we analyzed drug distribution as a function of blood vessel localization in tumor tissue. In order to explore distribution of the anti-cancer drugs afatinib, erlotinib, and sorafenib, a combined approach of matrix-assisted laser desorption/ionization (MALDI) drug imaging and immunohistochemical vessel staining was applied and examined by digital image analysis. Two xenograft models were investigated: (1) mice carrying squamous cell carcinoma (FaDu) xenografts (ntumor=13) were treated with afatinib or erlotinib, and (2) sarcoma (A673) xenograft bearing mice (ntumor=8) received sorafenib treatment. MALDI drug imaging revealed a heterogeneous distribution of all anti-cancer drugs. The tumor regions containing high drug levels were associated with a higher degree of vascularization than the regions without drug signals (p<0.05). When correlating the impact of blood vessel size to drug abundance in the sarcoma model, a higher amount of small vessels was detected in the tumor regions with high drug levels compared to the tumor regions with low drug levels (p<0.05). With the analysis of co-registered MALDI imaging and CD31 immunohistochemical data by digital image analysis, we demonstrate for the first time the potential of correlating MALDI drug imaging and immunohistochemistry. Here we describe a specific and precise approach for correlating histological features and pharmacokinetic properties of drugs at microscopic level, that will provide information for the improvement of drug design, administration formula or treatment schemes.Analytical Chemistry 09/2014; 86(21). DOI:10.1021/ac502177y · 5.83 Impact Factor
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ABSTRACT: Digital immunohistochemistry (IHC) is one of the most promising applications brought by new generation image analysis (IA). While conventional IHC staining quality is monitored by semi-quantitative visual evaluation of tissue controls, IA may require more sensitive measurement. We designed an automated system to digitally monitor IHC multi-tissue controls, based on SQL-level integration of laboratory information system with image and statistical analysis tools. Consecutive sections of TMA containing 10 cores of breast cancer tissue were used as tissue controls in routine Ki67 IHC testing. Ventana slide label barcode ID was sent to the LIS to register the serial section sequence. The slides were stained and scanned (Aperio ScanScope XT), IA was performed by the Aperio/Leica Colocalization and Genie Classifier/Nuclear algorithms. SQL-based integration ensured automated statistical analysis of the IA data by the SAS Enterprise Guide project. Factor analysis and plot visualizations were performed to explore slide-to-slide variation of the Ki67 IHC staining results in the control tissue. Slide-to-slide intra-core IHC staining analysis revealed rather significant variation of the variables reflecting the sample size, while Brown and Blue Intensity were relatively stable. To further investigate this variation, the IA results from the 10 cores were aggregated to minimize tissue-related variance. Factor analysis revealed association between the variables reflecting the sample size detected by IA and Blue Intensity. Since the main feature to be extracted from the tissue controls was staining intensity, we further explored the variation of the intensity variables in the individual cores. MeanBrownBlue Intensity ((Brown+Blue)/2) and DiffBrownBlue Intensity (Brown-Blue) were introduced to better contrast the absolute intensity and the colour balance variation in each core; relevant factor scores were extracted. Finally, tissue-related factors of IHC staining variance were explored in the individual tissue cores. Our solution enabled to monitor staining of IHC multi-tissue controls by the means of IA, followed by automated statistical analysis, integrated into the laboratory workflow. We found that, even in consecutive serial tissue sections, tissue-related factors affected the IHC IA results; meanwhile, less intense blue counterstain was associated with less amount of tissue, detected by the IA tools.