1. Developing a Statistical Method of Quantifying Vascular Response after Radiotherapy Michal Stankiewicz Medical Biophysics 3970Z Western University March 26, 2013 Supervised by Dr. Glenn Bauman and Dr. Slav Yartsev

2. Purpose and Motivation Brain Cancer Survival Radiotherapy technology Vascular response after radiotherapy on glioma tumours CT perfusions scans before and after radiotherapy Physiological information Coleman. M.P, et al, Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001. Br J Cancer, 2004. 90(7): p.1367-73.

3. Purpose and Motivation Highly heterogeneous after treatment Averaging response may not show a difference Waste of data Parametric Response Map (PRM) Voxel-by-voxel analysis Good predictor of patient survival Pre Post Galbán C.J., Ross B.D., et al. Nat Med, 2009;15(5):572-576

4. Objective Statistically quantifying voxels increased or decreased based on threshold tumour region of interest

5. Hypothesis Tumour regions will show lower vascular function after radiotherapy Blood volume Blood flow Permeability-surface area product (PS)

6. How CT Perfusion Works Tracer kinetics Iodinated contrast agent injected Serial CT images of each section Subtraction of baseline intensity Time-enhancement curve for each pixel Courtesy of Timothy Yeung Lee, T. Trends in Biotechnology, 2002;20(8):S3-S10

7. TDC Example Courtesy of Timothy Yeung

8. Parametric Maps PSBlood FlowBlood Volume Pre Post

9. Methods Parametric maps of BF, BV and PS MATLAB programvoxel-by-voxel analysis Radiosurgery treatment Single high dose CT perfusion scans 4-7 days after treatment Rat models Tumour Injection CT perfusion scans of developed tumour

10. Methods

11. Contour normal brain

12. Methods Difference map for PS (Pre - Post) Upper and lower thresholds Using pre treatment image to contour tumour ROI PrePost - =

13. Results BV difference in normal brain Lower 5 th percentile Upper 95 th percentile

14. Results Parametric response map of PS Showing pixels that significantly decreased, increased and no difference in PS Increased PS Decreased PS No difference

15. Results Response: Decreased PS in tumour ROI Response: Increased PS in tumour ROI No difference in tumour ROI response

16. Responses D4 SRS12 PRMPre MapPost Map SRS14 PS Response Decrease No change Increase

17. Future Work PrePost Peri-tumoural region Repeat for blood volume and flow

18. Thank you.