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Diffusion MRI is sensitive to brain tumor cell density

Diffusion MRI is sensitive to brain 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)

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Diffusion MRI is sensitive to brain tumor cell density

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  1. Diffusion MRI is sensitive to brain 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) • ADC (or mean diffusion) = cell density (“hypercellularity”) • ADC =  cell density (“hypocellularity”) Edema Necrotic Core Viable Tumor (Dark) ADC Map B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  2. Diffusion MRI is sensitive to brain tumor cell density • Tests at our laboratory have confirmed this relationship • 17 glioma patients (WHO II-IV) underwent diagnostic stereotactic biopsy • Biopsy sites were spatially matched to pre-operative ADC maps R2 = 0.7933; P < 0.001 From: Ellingson, et al. JMRI 2009, In Press SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  3. The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008) From: Ellingson, JMRI, 2009, In Press B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  4. SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  5. SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 From: Ellingson et al. J Neurooncol, 2009, In Press

  6. Early Detection of Brain Tumor Growth T1+C Contrast-Enhancement (white) FLAIR Hypercellular Regions (Blue) fDMs B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  7. fDMs in Brain Tumor Progression 3 mo. 6 mo. 9 mo. (Onset of symptoms) T1+C FLAIR fDM B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  8. fDMs in Progressive Disease (PD) Hypercellularity Hypercellularity Hypercellularity SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  9. fDM Results in Stable Disease (SD) Treatment: Radiation + Temozolomide SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  10. fDM Results in Responding Disease (RD) Treatment: Radiation + Temozolomide SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  11. fDM Results in Stable/Responding Disease (SD/RD) Hypocellularity Hypocellularity Hypocellularity SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  12. fDMs are an early biomarker for cytotoxic and new anti-angiogenic treatments B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Ellingson BM, J Neurooncol, Under Prep

  13. Results • “fDM Responders” have significantly longer TTP after standard Tx • fDMs are a better predictor than tumor grade SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  14. Results • “fDM Responders” have significantly longer survival on bevacizumab • fDMs are better predictors than grade, age, or mono/combined therapy SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  15. Graded fDMs Allow Visualization of Growing Tumor 1 Mo. 2 Mo. 3 Mo. 4 Mo. + Hypocellular + Hypercellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  16. Graded fDMs Allow Visualization of Growing Tumor 5 Mo. 7 Mo. 3 Mo. + Hypocellular + Hypercellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  17. Graded fDMs Allow Visualization of Growing Tumor 4 Mo. 5 Mo. 2 Mo. + Hypocellular + Hypercellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  18. Graded fDMs in Demyelination 3 Mo. 5 Mo. 7 Mo. 9 Mo. Hypercellular Hypocellular Macrophages & Inflammatory Cells Demyelination Biopsy Diagnosis = Demyelination (Multiple Sclerosis) B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  19. Graded fDMs: Radiation Necrosis vs. Tumor T1+C FLAIR Hypercellular Graded fDM Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  20. Graded fDMs: Radiation Induced Changes 2 Mo. 3 Mo. 5 Mo. 8 Mo. 14 Mo. 18 Mo. 21 Mo. 23 Mo. Hypercellular Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  21. Graded fDMs: Radiation Induced Changes 2 Mo. 4 Mo. 6 Mo. 14 Mo. 10 Mo. 18 Mo. Hypercellular Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  22. Graded fDMs Improve Tumor Localization/Grading in Stereotactic Needle Biopsy B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  23. Graded fDMs Improve Tumor Localizationand Grading in Stereotactic Needle Biopsy Biopsy (WHO II) 2 Lesions Hypercellular Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

  24. Graded fDMs Improve Tumor Localization for Resection Resection Cavity Hypercellular Only 10% of Hypercellular regions were removed! Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

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