1. Functional Diffusion Maps (fDMs) for Brain Tumor Treatment Response Monitoring Benjamin M. Ellingson, Ph.D. Assistant Professor of Radiology Dept. of Radiological Sciences David Geffen School of Medicine at UCLA B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

2. Diffusion MRI is sensitive to tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008; Ellingson, 2010)  ADC (or mean diffusion) =  cell density (“hypercellularity”)  ADC =  cell density (“hypocellularity”) Viable Tumor (Dark) Necrotic Core Edema ADC Map B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

3. ADC correlates with brain tumor cell density Untreated glioma patients (WHO II-IV) underwent diagnostic stereotactic biopsy (n = 17) biopsy sites were spatially matched to the pre-operative ADC map R 2 = 0.7933; P < 0.001 ADC Sensitivity = 1.01 x 10 -7 [mm 2 /s]/[nuclei/mm 2 ] From: Ellingson BM et al., J Magn Reson Imaging, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

4. From: Ellingson, JMRI, 2009, In Press The Functional Diffusion Map (fDM) (Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2009; 2010; 2011) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

5. From: Ellingson, JMRI, 2009, In Press B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011 The Functional Diffusion Map (fDM) (Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2009; 2010; 2011)

6. Early Detection of Brain Tumor Growth T1+C FLAIR fDMs Contrast-Enhancement (white) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

7. fDMs in Brain Tumor Progression T1+C FLAIR fDM 3 mo.6 mo.9 mo. (Onset of symptoms) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

8. From: Ellingson, ISMRM, 2009; SNO, 2009 fDMs in Progressive Disease (PD)  Hypercellularity B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

9. From: Ellingson, ISMRM, 2009; SNO, 2009 fDM Results in Stable/Responding Disease (SD/RD)  Hypocellularity B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

10. From: Ellingson, ISMRM, 2009; SNO, 2009 fDMs May Reflect Molecular/Genetic Phenotypes MGMT(+) MGMT(-) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

11. From: Ellingson, ISMRM, 2009; SNO, 2009 fDMs May Reflect Molecular/Genetic Phenotypes B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

12. (n = 50 Total Patients) Spearman Corr. Coeff. R = 0.4350, P = 0.0016 Clinical fDM Sensitivity/Specificity WHO Grade From: Ellingson BM et al., ISMRM, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

13. (n = 50 Total Patients) Pearson Corr. Coeff. R 2 = 0.8586, P < 0.0001 Clinical fDM Sensitivity/Specificity Neurological Status From: Ellingson BM et al., ISMRM, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

14. fDMs Before/After Radiotherapy N = 94

15. B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011 fDMs Before/After Bevacizumab N = 77

16. Graded fDMs B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

17. Graded fDMs: Tumor Invasion Beyond FLAIR B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

18. Graded fDMs for StealthStation™ Biopsy Localization B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

19. Hypercellular Hypocellular Macrophages & Inflammatory Cells Demyelination Graded fDMs in Differential Diagnosis Tumor vs. Demyelination Biopsy Diagnosis = Demyelination (Multiple Sclerosis) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

20. Graded fDMs – Radiation Necrosis Hypercellular Hypocellular T1+C FLAIR Graded fDM B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

21. Stereotactic fDMs Using a Neuroanatomical Atlas Anatomy Label Map Overlaid On T1 Atlas B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011