Automatic analysis of angiogenic hotspots in histological whole slide images

Master thesis in Medical Physics

by Jakob Nikolas Kather

supervised by: PD Dr. Frank Zöllner, Dr. Cleo-Aron Weis

Jakob Nikolas Kather I Slide 2 I 05/01/2023

• Pathophysiology: all solid tumors need blood supply

• Example: Colorectal cancer

• More blood vessels correlate to higher mortality

Tumor angiogenesis Introduction

Jakob Nikolas Kather I Slide 3 I 05/01/2023

Microscopy and blood vessel immunostaining Introduction

Jakob Nikolas Kather I Slide 4 I 05/01/2023

Colorectal cancer: whole slide imaging

2 m

m

Introduction

Jakob Nikolas Kather I Slide 5 I 05/01/2023

Aim of this study

Use image analysis to make this procedure objective and reproducible

State of the art Introduction

Jakob Nikolas Kather I Slide 6 I 05/01/2023

Image segmentation Methods

Jakob Nikolas Kather I Slide 7 I 05/01/2023

Blood vessel map on whole slide image Methods

Jakob Nikolas Kather I Slide 8 I 05/01/2023

Comparison to random pattern Methods

Jakob Nikolas Kather I Slide 9 I 05/01/2023

Continuous density function Results

Jakob Nikolas Kather I Slide 10 I 05/01/2023

F(x,y)

x,y

ρ

μ

σ

obs

CSR

probability function

spatial dimensions

density function

global mean

global std. dev.

observed data

random data

Normalization / Noise removal Results

Jakob Nikolas Kather I Slide 11 I 05/01/2023

standard deviations

Hotspot probability map Results

Jakob Nikolas Kather I Slide 12 I 05/01/2023

Black contours = hotspots selected by blinded observer (# primary hotspot)Color bar refers to hotspot probability function overlay (* level of significance)

Comparison to human observer Results

Jakob Nikolas Kather I Slide 13 I 05/01/2023

Optimized workflow Conclusion

Jakob Nikolas Kather I Slide 14 I 05/01/2023

Multivariate maps Outlook

Jakob Nikolas Kather I Slide 15 I 05/01/2023

Thank you!

PD Dr. Frank Zöllner

Dr. Cleo-Aron Weis, MSc

Prof. Dr. Lothar Schad

Prof. Dr. Alexander Marx

Jakob Nikolas Kather I Slide 16 I 05/01/2023

Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 2006;94(12):1823-32.

Baddeley, A., & Turner, R. (2005). Spatstat: an R package for analyzing spatial point patterns. J Stat Softw, 12(6), 1–42.

Gelfand, A. E., Diggle, P., Guttorp, P., & Fuentes, M. (2010). Handbook of spatial statistics. Boca Raton, FL, USA: CRC press.

Kather, J. N., Marx, A., Reyes-Aldasoro, C. C., Schad, L. R., Zöllner, F. G., & Weis, C.-A. (2015). Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images. Oncotarget. Epub ahead of print 2015 Jun 8.

References