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

• 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




• Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly(Young, 2000; Baron, 2007)






• Pathogenesis(Baron, 2007)









DiscDegeneration

(Photos courtesy of Arin Ellingson, University of Minnesota)







DiscDegeneration

IncreasedStresses onEndplates







DiscDegeneration


SubperiostealBone and OsteophyticBar Formation







DiscDegeneration



EncroachmentOn Spinal Cord







DiscDegeneration



EncroachmentOn Spinal Cord

NeurologicalImpairment



Bernhardt, J Bone Joint Surg, 1993

• Heterogeneity in CSM progression:

Need for a Sensitive Imaging Biomarker





Bernhardt, J Bone Joint Surg, 1993




Neurologically Intact Neurologically Impaired


• 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)







1990)

• Diffusion tensor imaging (DTI) has shown promise as a biomarker for spinal cord health







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)







1990)


– More sensitive to specific abnormalities of the cord than conventional MR (Schwartz, 2005;

Herrera, 2007; Ellingson, 2010)







1990)


– 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)





• 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)


– 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



Hypotheses


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



2009)

2. Fractional Anisotropy will be reduced at the site of compression in neurologically-impaired patients (Demir, 2003; Mamata, 2005; Facon, 2005)

Hypotheses



2009)


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



2009)


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


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

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

SS

PE

RO

FoV

rFoV

Reduced Field of Excitation in PE uses same direction as rFOV (receive)

Reduced FoV Full FoV

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

http://www.trackvis.org/

Results


Conventional MR and Morphometry

Stenosis Stenosis + MyelopathyNormal Control

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

Results


* SNR FWHM = 20mm

Results


Mean Diffusivity

Results


Fractional Anisotropy

Results


FA Color Map

Results


Results


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


DTI vs. mJOA

R2 = 0.4248P = 0.0115 R2 = 0.6006

P = 0.0011

Results


Tractography

Control CSM CSM

Results


Tractography

Results


Tractography

P < 0.05 vs. Stenosis

P < 0.05 vs. Normal

Results


Tractography vs. mJOA

R2 = 0.3970P = 0.0067

Conclusions


1. 2D spatially-selective RF excitation pulse + reduced FOV EPI readout reduced echo train length / less distortion = High Quality Spinal Cord DTI

Conclusions



2. FA is reduced and MD is increased at the site of compression

Conclusions




3. lADC (parallel ADC) is reduced in neurologically-impaired patients whereas tADC (transverse ADC) is elevated in stenosis w/o myelopathy patients

Conclusions






Conclusions






DTI shows great potential as a biomarker for degree of neurological impairment and

may be useful for choosing surgical candidates

Thank You!


disclosures

Documents

cervical spine spondylosis

radiological sciences

disclosurespaid consultant

medqia llcpaid consultant

agios pharmaceuticals

siemens medical systemsb