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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 Women Men Purpose and Motivation Testis Hodgkin's lymphoma Melanoma Bladder Larynx Prostate NHL Colon Rectum Kidney Leukaemia Multiple myeloma Brain Stomach Oesophagus Lung Pancreas Melanoma Hodgkin's lymphoma Breast Uterus Cervix Bladder NHL Rectum Colon Kidney Leukaemia Ovary Multiple myeloma Brain Stomach Oesophagus Lung Pancreas 95% 84% 78% 71% 67% 61% 51% 46% 45% 45% 38% • Brain Cancer Survival • Radiotherapy • 24% 13% 12% 7% 6% 3% 90% 83% 79% 76% 68% 61% 52% 48% 45% 43% 36% 34% 22% 15% 13% 8% 6% 2% Five-year relative survival • • 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. Purpose and Motivation Pre Post • 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 surviva Galbán C.J., Ross B.D., et al. Nat Med, 2009;15(5):572-576 Objective Statistically quantifying voxels • increased or decreased based on threshold • tumour region of interest Hypothesis • Tumour regions will show lower vascular function after radiotherapy • Blood volume • Blood flow • Permeability-surface area product (PS) 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 Lee, T. Trends in Biotechnology, 2002;20(8):S3-S10 Courtesy of Timothy Yeung TDC Example 70 Tumor 60 Brain Enhancement (HU) 50 40 30 20 10 0 -10 -20 0 50 100 150 200 Time (s) Courtesy of Timothy Yeung 250 300 350 Parametric Maps Blood Flow Blood Volume Pre Post PS Methods Rat models Tumour Injection CT perfusion scans of developed tumour Radiosurgery treatment Single high dose CT perfusion scans 4-7 days after treatment Parametric maps of BF, BV and PS MATLAB program voxel-by-voxel analysis Methods Methods • Contour normal brain Methods Pre = Post Difference map for PS (Pre - Post) • Upper and lower thresholds • Using pre treatment image to contour tumour ROI Results BV difference in normal brain Average Thresholds of Normal Brain PS 3.00 Lower 5th percentile Upper 95th percentile 2.00 1.00 PS (ml/100 g) 0.00 -1.00 -2.00 -3.00 95th Percentile 5th Percentile Results Increased PS No difference Decreased PS Parametric response map of PS • Showing pixels that significantly decreased, increased and no difference in PS Results Pixel Distribution of ΔPS in PRM Tumour ROI 100% Percentage 80% 60% Increased PS No Difference in PS Decreased PS 40% 20% 0% SRS11 SRS14 A1a Response: Decreased PS in tumour ROI SRS13 A1c D4 Subject SRS5 SRS12 Response: Increased PS in tumour ROI SRS6 SRS3 SRS2 No difference in tumour ROI response Responses PS Response Pre Map Post Map PRM Decrease SRS14 No change SRS12 Increase D4 Future Work • Repeat for blood volume and flow • Peri-tumoural region Pre Post Thank you.