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Disclosures

Disclosures. Paid Consultant, MedQIA LLC Paid Consultant, Agios Pharmaceuticals, Inc. Consultant, Genentech Consultant, Siemens Medical Systems. B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011.

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Disclosures

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  1. Disclosures Paid Consultant, MedQIA LLC Paid Consultant, Agios Pharmaceuticals, Inc. Consultant, Genentech Consultant, Siemens Medical Systems B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  2. Diffusion MR Characteristics of theCentral Nervous System • Apparent diffusion coefficient (ADC) measured clinically reflects extracellular water • ADC is dependent on tumor cell density (Ellingson, 2010; Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008 •  Cell Density (hypercellular) =  ADC •  Cell Density (hypocellular) =  ADC From: Ellingson, J Magn Reson Imaging, 2010 Edema Necrotic Core Viable Tumor (Dark) ADC Map B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  3. The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2010) From: Ellingson, JMRI, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  4. Graded fDMs Allow Visualization and Quantification of Growing Tumor + Hypocellular + Hypercellular From: Ellingson, JMRI, 2010 Biological Calibration B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  5. Graded fDMs Allow Better Visualization of Growing Tumor + Hypocellular + Hypercellular B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  6. What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  7. What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  8. What about anti-angiogenic therapy? Apparent diffusion coefficient (ADC) measured clinically reflects extracellular water Large changes in ADC after anti-angiogenic therapy reflect (largely) reduction in edema Subtle decreases in ADC after anti-angiogenic treatment are likely to contain solid / infiltrating tumor B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  9. What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  10. What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  11. What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  12. What about anti-angiogenic therapy? Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  13. What about anti-angiogenic therapy? Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure 2. Graded fDMs  tumor growth  greater risk of failure B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  14. What about anti-angiogenic therapy? Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure 2. Graded fDMs  tumor growth  greater risk of failure 3. Graded fDMs + pre-treatment ADC + T1+C  active tumor burden  GREATEST RISK (BEST PREDICTOR) Pope, Radiology, 2009; Pope, AJNR, 2011 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  15. Methods Patients N = 77 patients - Pathology confirmed GBM with recurrence confirmed via histology or clinical features - Regularly treated every 2 weeks per cycle with becacizumab (5-10 mg/kg) - Baseline & minimum of one follow-up with high-quality diffusion MRI MRI Clinical MR sequences on 1.5T T2w, FLAIR, T1w, T1+C 3-5mm slice thickness Diffusion MRI w/ twice refocused spin echo preparation ADC calculated from b=0 and b=1000 s/mm2 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  16. Methods • Image Registration • All images registered to Baseline T1 weighted images • Mutual information + 12 dof transformation • Graded fDM Calculation • - Voxel-wise subtraction • Each voxel classified according to relative difference from previous calibration studies From: Ellingson, JMRI, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  17. Methods • Traditional fDM  ΔADC beyond 0.4 um2/ms B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  18. Methods • Traditional fDM  ΔADC beyond 0.4 um2/ms • Graded fDM  ΔADC between 0.25 and 0.4 um2/ms (7.5% probability of occurring randomly) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  19. Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  20. Results Conventional response does not predict survival From: Ellingson, Neuro Onc, 2011 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  21. Results Conventional response does not predict survival B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  22. Results Graded fDM regions are localized to post-treatment contrast enhancement B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  23. Results Traditional and graded fDMs both predict survival B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  24. Results T1+C is better than FLAIR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  25. Results Graded fDMs are better than traditional fDMs B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  26. Results Graded fDMs in T1+C B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  27. Results ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Chi-squared goodness of fit, P < 0.05 Between CE and graded fDMs For 46 of 77 patients B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  28. Results ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Chi-squared goodness of fit, P < 0.05 Between CE and graded fDMs For 46 of 77 patients B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  29. Results ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Graded fDMs  FILTER Chi-squared goodness of fit, P < 0.05 Between T1+C and graded fDMs For 46 of 77 patients B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  30. Results Graded fDMs + Pre-Tx ADC Characteristics B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  31. Results Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  32. Results Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  33. Summary Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  34. Summary Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  35. Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS Conclusions B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  36. Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS Subtle changes in ADC after anti-angiogenic therapy w/in T1+C may reflect active tumor burden Conclusions B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  37. Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS Subtle changes in ADC after anti-angiogenic therapy w/in T1+C may reflect active tumor burden Conclusions Graded fDMs + Pre-Tx ADC Characteristics in T1+C BEST PREDICTOR Median Survival Advantage of 7 months B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  38. Radiology Whitney Pope, M.D., Ph.D. Dieter Enzmann, M.D. Jonathan Goldin, M.D. MedQIA Neurology/Neuro-Oncology Timothy Cloughesy, M.D. Albert Lai, M.D., Ph.D. Phioanh (Leia) Nghiemphu, M.D. Thank You! • Neurosurgery • Linda Liau, M.D. • Bob Shafa, M.D. • Antonio DeSalles, M.D. • Pathology • Paul Mischel, M.D. • Bill Yong, M.D. • Medical College of Wisconsin • Kathleen Schmainda, Ph.D. • Peter LaViolette, B.S. • David Geffen School of Medicine • Taryar Zaw, B.S. • Korosh Neini, M.D. • Bobby Harris, B.S. • Carissa White, B.S. B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

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