We started digital pathology research in 2010 with image analysis-based quantification1, 2 and exploring the benefits of multivariate analytics of image analysis data to generate combined image-based biomarkers3, 4. Further, we performed accuracy and calibration experiments for image analysis-based quantification5, 6, 7, 8.

In 2015, we proposed a methodology based on hexagonal tiling of image analysis data to quantify intra-tumor heterogeneity of biomarker expression9; this allowed to generate rich data set to compute spatial indicators. We conceptualized this approach as “comprehensive immunohistochemistry”10. The heterogeneity indicators were demonstrated in later studies as independent prognostic factors, often exceeding the informative value of the average level of the biomarker expression11, 12.

In 2020, we published another hexagonal grid-based methodology to automatically detect tumor-host interface zone and compute immune cell density profile across the zone13; this actually measures the “willingness” of immune cells to enter the tumor (immunogradient) and provides independent prognostic value11, 13, 14. Compared to other methods proposed to measure immune response in the tumor microenvironment, the interface zone immunogradient provides quantitative directional assessment in the very frontline of tumor-host interaction. 

Patent applications

patentas 1Lithuanian name - Automatizuotas naviko ir stromos sąsajos zonos nustatymas, skirtas naviko atsako įvertinimui naudojant imunogradientinius indikatorius
English name -  Automated Tumour-Stroma Interface Zone Detection for Anti-Tumour Response Assessment by Immunogradient Indicators
Patent application number: LT 2019 509
Date of submission: April 09, 2019
Inventors: Rasmusson A, Zilenaite D, Nestarenkaite A, Augulis R, Laurinavicius A.
Applicant - University of Vilnius
About 2020-09-17 Spatial statistics extract subvisual features
Source of information: VU

English name
: Computer-implemented process on an image of a biological sample

Patent application number: PCT/EP2019/067180

Date of submission: 2019-06-27
Inventors: B. Plancoulaine, L. Poulain, N. Elie, A. Laurinavicius

Applicants: University of Caen Normandy, University of Vilnius, National Institute of Health, Center Francois Baclesse


[1] Brazdziute E, Laurinavicius A: Digital pathology evaluation of complement C4d component deposition in the kidney allograft biopsies is a useful tool to improve reproducibility of the scoring. Diagnostic Pathology 2011. http://www.diagnosticpathology.org/content/pdf/1746-1596-6-S1-S5.pdf
[2] Laurinaviciene A, Dasevicius D, Ostapenko V, Jarmalaite S, Lazutka J, Laurinavicius A: Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays. Diagnostic Pathology 2011. http://www.diagnosticpathology.org/content/pdf/1746-1596-6-87.pdf
[3] Laurinavicius A, Laurinaviciene A, Ostapenko V, Dasevicius D, Jarmalaite S, Lazutka J: Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data. Diagnostic Pathology 2012. http://www.diagnosticpathology.org/content/pdf/1746-1596-7-27.pdf
[4] Laurinavicius A, Green AR, Laurinaviciene A, Smailyte G, Ostapenko V, Meskauskas R, Ellis IO: Ki67/SATB1 ratio is an independent prognostic factor of overall survival in patients with early hormone receptor-positive invasive ductal breast carcinoma. Oncotarget 2015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747395/pdf/oncotarget-06-41134.pdf
[5] Laurinavicius A, Plancoulaine B, Laurinaviciene A, Herlin P, Meskauskas R, Baltrusaityte I, Besusparis J, Dasevicius D, Elie N, Iqbal Y, Bor C, Ellis IO: A methodology to ensure and improve accuracy of Ki67 labelling index estimation by automated digital image analysis in breast cancer tissue. Breast Cancer Research 2014. http://www.breast-cancer-research.com/content/pdf/bcr3639.pdf
[6] Laurinaviciene A, Plancoulaine B, Baltrusaityte I, Meskauskas R, Besusparis J, Lesciute-Krilaviciene D, Raudeliunas D, Iqbal Y, Herlin P, Laurinavicius A: Digital immunohistochemistry platform for the staining variation monitoring based on integration of image and statistical analyses with laboratory information system. Diagn Pathol 2014. http://www.ncbi.nlm.nih.gov/pubmed/25565007
[7] Plancoulaine B, Laurinaviciene A, Meskauskas R, Baltrusaityte I, Besusparis J, Herlin P, Laurinavicius A: Digital immunohistochemistry wizard: image analysis-assisted stereology tool to produce reference data set for calibration and quality control. Diagn Pathol 2014. http://www.ncbi.nlm.nih.gov/pubmed/25565221://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305978/pdf/1746-1596-9-S1-S8.pdf
[8] Besusparis J, Plancoulaine B, Rasmusson A, Augulis R, Green AR, Ellis IO, Laurinaviciene A, Herlin P, Laurinavicius A: Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer. Diagnostic Pathology 2016. https://pubmed.ncbi.nlm.nih.gov/27576949/
[9] Plancoulaine B, Laurinaviciene A, Herlin P, Besusparis J, Meskauskas R, Baltrusaityte I, Iqbal Y, Laurinavicius A: A methodology for comprehensive breast cancer Ki67 labeling index with intra-tumor heterogeneity appraisal based on hexagonal tiling of digital image analysis data. Virchows Archiv 2015. https://link.springer.com/article/10.1007/s00428-015-1865-x
[10] Laurinavicius A, Plancoulaine B, Herlin P, Laurinaviciene A: Comprehensive Immunohistochemistry: Digital, Analytical and Integrated. Pathobiology 2016. <Go to ISI>://WOS:000375025100012 https://www.karger.com/Article/Pdf/442389
[11] Zilenaite D, Rasmusson A, Augulis R, Besusparis J, Laurinaviciene A, Plancoulaine B, Ostapenko V, Laurinavicius A: Independent Prognostic Value of Intratumoral Heterogeneity and Immune Response Features by Automated Digital Immunohistochemistry Analysis in Early Hormone Receptor-Positive Breast Carcinoma. Front Oncol 2020. https://www.ncbi.nlm.nih.gov/pubmed/32612954https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308549/pdf/fonc-10-00950.pdf
[12] Laurinavicius A, Plancoulaine B, Rasmusson A, Besusparis J, Augulis R, Meskauskas R, Herlin P, Laurinaviciene A, Muftah AAA, Miligy I, Aleskandarany M, Rakha EA, Green AR, Ellis IO: Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma. Virchows Archiv 2016. https://link.springer.com/article/10.1007%2Fs00428-016-1907-z
[13] Rasmusson A, Zilenaite D, Nestarenkaite A, Augulis R, Laurinaviciene A, Ostapenko V, Poskus T, Laurinavicius A: Immunogradient indicators for anti-tumor response assessment by automated tumor-stroma interface zone detection. Am J Pathol 2020. https://www.sciencedirect.com/science/article/pii/S0002944020301267#appsec1https://www.ncbi.nlm.nih.gov/pubmed/32194048
[14] Nestarenkaite A, Fadhil W, Rasmusson A, Susanti S, Hadjimichael E, Laurinaviciene A, Ilyas M, Laurinavicius A: Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status. Cancers (Basel) 2020. https://www.ncbi.nlm.nih.gov/pubmed/33050344https://res.mdpi.com/d_attachment/cancers/cancers-12-02902/article_deploy/cancers-12-02902-v2.pdf

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