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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. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  3. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  4. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954)and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  5. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) Disc Degeneration (Photos courtesy of Arin Ellingson, University of Minnesota) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  6. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) Disc Degeneration Increased Stresses on Endplates B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  7. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954)and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) Disc Degeneration Increased Stresses on Endplates Subperiosteal Bone and Osteophytic Bar Formation B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  8. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) Disc Degeneration Increased Stresses on Endplates Subperiosteal Bone and Osteophytic Bar Formation Encroachment On Spinal Cord B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  9. Cervical Spondylotic Myelopathy • Degenerative changes in the cervical spine (spondylosis) occurs >50% of people over 55(Hughes,1965; Irvine, 1965; Pallis, 1954) and >75% of people over age 65 (Larocca, 1988) • Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young,2000; Baron, 2007) • Pathogenesis(Baron, 2007) Disc Degeneration Increased Stresses on Endplates Subperiosteal Bone and Osteophytic Bar Formation Encroachment On Spinal Cord Neurological Impairment B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  10. Cervical Spondylotic Myelopathy Bernhardt, J Bone Joint Surg, 1993 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  11. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  12. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: Bernhardt, J Bone Joint Surg, 1993 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  13. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: Neurologically Intact Neurologically Impaired B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  14. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  15. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  16. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) • Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  17. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) • Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health • Sensitive to tissue integrity and architecture (Schwartz, 2005; Ford, 1994) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  18. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) • Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health • Sensitive to tissue integrity and architecture (Schwartz, 2005; Ford, 1994) • More sensitive to specific abnormalities of the cord than conventional MR (Schwartz, 2005; Herrera, 2007; Ellingson, 2010) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  19. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) • Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health • Sensitive to tissue integrity and architecture (Schwartz, 2005; Ford, 1994) • More sensitive to specific abnormalities of the cord than conventional MR (Schwartz, 2005; Herrera, 2007; Ellingson, 2010) • Preliminary results suggest DTI might be of diagnostic utility in CSM (Bammer, 2000; Ries, 2000; Demir, 2003; Facon, 2005; Mamata, 2005; Hori, 2006; Ellingson, 2010) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  20. Need for a Sensitive Imaging Biomarker • Heterogeneity in CSM progression: • Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005) • Conventional MRI findings do not consistently correlate with outcomes after treatment (Morio, 1994; 2001; Yukawa, 2007; 2008; Matsuda, 1991; Mastronardi, 2007; Matsumoto, 2000; Fernandez de Rota, 2007; Puzzilli, 1999; Takahashi, 1989; Mehalic, 1990) • Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health • Sensitive to tissue integrity and architecture (Schwartz, 2005; Ford, 1994) • More sensitive to specific abnormalities of the cord than conventional MR (Schwartz, 2005; Herrera, 2007; Ellingson, 2010) • Preliminary results suggest DTI might be of diagnostic utility in CSM (Bammer, 2000; Ries, 2000; Demir, 2003; Facon, 2005; Mamata, 2005; Hori, 2006; Ellingson, 2010) • However, spinal cord DTI suffers from many “issues” • Small size of cord • Motion artifact • Magnetic susceptibility distortions from surrounding bone • Chemical shift artifacts from fat B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  21. Hypotheses • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI(Saritas, 2008; Finsterbusch, 2009) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  22. Hypotheses • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI(Saritas, 2008; Finsterbusch, 2009) • Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  23. Hypotheses • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI(Saritas, 2008; Finsterbusch, 2009) • Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005) • lADC (parallel ADC) will be reduced in neurologically-impaired patients (Ellingson, 2008), whereas stenosis w/o myelpathy will have elevated tADC (transverse ADC) (Song, 2002; Sun, 2003; Klawiter, 2011) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  24. Hypotheses • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI(Saritas, 2008; Finsterbusch, 2009) • Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005) • lADC (parallel ADC) will be reduced in neurologically-impaired patients (Ellingson, 2008), whereas stenosis w/o myelpathy will have elevated tADC (transverse ADC) (Song, 2002; Sun, 2003; Klawiter, 2011) • DTI parameters correlate with neurological impairment (mJOA) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  25. Methods • Patients: • 9 neurologically intact control subjects (age range 30 – 54, mean = 36) • 12 patients with cervical stenosis with (n = 7) and without (n = 5) mild myelopathy • All patients gave approved written consent to participate • All procedures were approved by the IRB at UCLA B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  26. Methods • MRI: • 3T MR System (Siemens Trio TIM) & array coil • Sagittal and Axial T1w and T2w • DTI was acquired in 6 directions, b = 0 and 500 s/mm2 • NEX = 15 • TE = 67ms TR = 3000ms • ~ 1mm x 1mm in-plane resolution • Slice thickness = 4mm B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  27. PE SS RO Methods • 2D RF pulse used for slab excitation: • Duration 11.7 ms • 25 lines / echo spacing 0.45 ms • EPI trajectory with ramp sampling • 48 x 128 matrix, 53 x 140 mm2 • Reduced Field of Excitation in PE uses same direction as rFOV (receive) Reduced FoV Full FoV FoV rFoV B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  28. Methods • Tractography: • Diffusion Toolkit and TrackVis (MGH) www.trackvis.org • “Tensorline” propagation algorithm (Weinstein, 1999), angle threshold = 90 degrees • ROI placed to encompass whole cord B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  29. Results Conventional MR and Morphometry Normal Control Stenosis + Myelopathy Stenosis B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  30. Results Conventional MR and Morphometry * Two-way ANOVA (Group, P < 0.0001; Level, P < 0.0001) * Stenosis vs. Normal, P < 0.05 for levels C2-3 through C6-7 * No detected diff for Myelopathy B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  31. Results * SNR FWHM = 20mm B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

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

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

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

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

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

  37. Results DTI vs. Compression Site Two-way ANOVA; Groups, P < 0.0001 Level of Compression: Normal vs. Stenosis, P < 0.001 Normal vs. Stenosis+Myelopathy, P < 0.001 Stenosis vs. Stenosis+Myelopathy, P < 0.05 Two-way ANOVA Level of Compression: Normal vs. Stenosis, P < 0.001 Normal vs. Stenosis+Myelopathy, P < 0.001 Stenosis vs. Stenosis+Myelopathy, N.S. B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  38. Results DTI vs. mJOA R2 = 0.4248 P = 0.0115 R2 = 0.6006 P = 0.0011 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

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

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

  41. Results Tractography P < 0.05 vs. Normal P < 0.05 vs. Stenosis B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  42. Results Tractography vs. mJOA R2 = 0.3970 P = 0.0067 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  43. Conclusions • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  44. Conclusions • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI • FA is reduced and MD is increased at the site of compression B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  45. Conclusions • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI • FA is reduced and MD is increased at the site of compression • lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  46. Conclusions • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI • FA is reduced and MD is increased at the site of compression • lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients • DTI parameters correlate with neurological impairment (mJOA) B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  47. Conclusions • 2D spatially-selective RF excitation pulse + reduced FOV EPI readout  reduced echo train length / less distortion = High Quality Spinal Cord DTI • FA is reduced and MD is increased at the site of compression • lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients • DTI parameters correlate with neurological impairment (mJOA) DTI shows great potential as a biomarker for degree of neurological impairment and may be useful for choosing surgical candidates B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

  48. Thank You! B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011

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