Jan 11, 2016
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
• 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
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DiscDegeneration
(Photos courtesy of Arin Ellingson, University of Minnesota)
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DiscDegeneration
IncreasedStresses onEndplates
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DiscDegeneration
IncreasedStresses onEndplates
SubperiostealBone and OsteophyticBar Formation
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DiscDegeneration
IncreasedStresses onEndplates
SubperiostealBone and OsteophyticBar Formation
EncroachmentOn Spinal Cord
• 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)
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DiscDegeneration
IncreasedStresses onEndplates
SubperiostealBone and OsteophyticBar Formation
EncroachmentOn Spinal Cord
NeurologicalImpairment
Cervical Spondylotic Myelopathy
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Bernhardt, J Bone Joint Surg, 1993
• Heterogeneity in CSM progression:
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• Heterogeneity in CSM progression:
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Bernhardt, J Bone Joint Surg, 1993
• Heterogeneity in CSM progression:
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Neurologically Intact Neurologically Impaired
• Heterogeneity in CSM progression:
• Surgeons are more likely to operate on the basis of imaging even without clinical impairment (Irwin, 2005)
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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)
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• 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
Need for a Sensitive Imaging Biomarker
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Hypotheses
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 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)
Hypotheses
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 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)
2. Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005)
Hypotheses
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 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)
2. Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005)
3. 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)
Hypotheses
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 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)
2. Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005)
3. 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)
4. DTI parameters correlate with neurological impairment (mJOA)
• 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
Methods
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Methods
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
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
Methods
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
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
SS
PE
RO
FoV
rFoV
Reduced Field of Excitation in PE uses same direction as rFOV (receive)
Reduced FoV Full FoV
Methods
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
• Tractography:
• Diffusion Toolkit and TrackVis (MGH) www.trackvis.org
– “Tensorline” propagation algorithm (Weinstein, 1999), angle threshold = 90 degrees
– ROI placed to encompass whole cord
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Conventional MR and Morphometry
Stenosis Stenosis + MyelopathyNormal Control
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
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
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
* SNR FWHM = 20mm
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Mean Diffusivity
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Fractional Anisotropy
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
FA Color Map
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DTI vs. Compression Site
Two-way ANOVA; Groups, P < 0.0001
Level of Compression:Normal vs. Stenosis, P < 0.001Normal vs. Stenosis+Myelopathy, P < 0.001
Stenosis vs. Stenosis+Myelopathy, P < 0.05
Two-way ANOVA
Level of Compression:Normal vs. Stenosis, P < 0.001Normal vs. Stenosis+Myelopathy, P < 0.001
Stenosis vs. Stenosis+Myelopathy, N.S.
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
DTI vs. mJOA
R2 = 0.4248P = 0.0115 R2 = 0.6006
P = 0.0011
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Tractography
Control CSM CSM
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Tractography
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Tractography
P < 0.05 vs. Stenosis
P < 0.05 vs. Normal
Results
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
Tractography vs. mJOA
R2 = 0.3970P = 0.0067
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI
2. FA is reduced and MD is increased at the site of compression
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI
2. FA is reduced and MD is increased at the site of compression
3. lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI
2. FA is reduced and MD is increased at the site of compression
3. lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients
4. DTI parameters correlate with neurological impairment (mJOA)
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011
1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI
2. FA is reduced and MD is increased at the site of compression
3. lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients
4. 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
Thank You!
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA ISMRM, Montreal, 2011