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NMR of SCI
Using Nuclear Magnetic Resonance to Explore Spinal Cord Injury
Outline
Goals
Spinal Cord Injury (SCI) Nuclear Magnetic Resonance (NMR)
Methods Results to date
Summary Time line
Goals
Big Picture Goal Non-invasive assessment of
SCI Progression of SCI Treatment of SCI
Why NMR non-invasive assessment of
Gross physical changes Changes in water distribution Changes in metabolites
Repeatable
Progression of SCI
Primary Injury Severity Location
Secondary Injury Vascular Changes Cellular Changes Biochemical Changes
Incomplete tetraplegia
Complete paraplegia
Incomplete paraplegia
Complete tetraplegia
Interventions
Immobilization Prevents further damage
Drugs Methylpresnisolone
Surgery Remove damaged tissue
Physiotherapy Train
Functional Electronic Stimulation Intra Spinal Micro Stimulation
NMR Spin
Spin basic property of matter 1H, 13C, 31P all have an observable magnetic
moment This project deals with protons 1H The protons precess in a magnetic field at a frequency
proportional to the field strength B0
B0
Nucleus
M
ω0=−γ B0
NMR
An orthogonal field B1 at the same
frequency can tip the magnetic moment into the transverse plane
In the transverse plane the the motion of the magnetic moment create a radio frequency signal at a frequency proportional to the B
0 they are
experiencing
y'
z'
x'
M
B1
θ
refference frame rotating at ω0
NMR Relaxation
T1
Longitudinal relaxation Return to thermal
equilibrium T
2
Transverse relaxation Dipole dipole interactions
T2*
T2 plus Static
inhomogeneities y'
z'
x' M
refference frame rotating at ω0
Magnetic Resonance Imaging
Gradient Echo
B1 Excitation
Slice Defining Gradient
Phase Encoding Gradient
Frequency Encoding Gradient
Acquisition Signal
B (r)
B (p)
B (q)
Magnetic Resonance Spectroscopy
Chemical Shift J-coupling
ppm
C
C
O
H
HH
H
MRI Preoperative
Gradient Echo Sequence TE 25 ms, TR 850 ms Ernst angle 0.31 mm/pixel in plane 4 mm slice thickness
Custom Surface Coil
A Surface Coil
tuningcapacitor
matchingcapacitor Receiver
AndPulse
Generator
capacitor (C)inductance (L) variable capacitor
Key
TR
TE
MRI Micro Wires
Spin Echo TE 34 ms, TR 2000 ms 0.39 mm/pixel in plane 1.5 mm slice thickness
B1
SliceSelect Gradient
Phase Encode Gradient
FrequencyEncodeGradient
AcquisitionSignal
90o180o
Water Compartmentalization
Separates myelin water from other water TORO coils CPMG imaging TE 7-300 ms 10mm rostral 12mm, 21mm,35mm caudal
B1 Excitation
Phase Encoding Gradient
Frequency Encoding Gradients
Acquisition Signals
Slice Defining Gradients
180o90o 180o180o 180o
Transverse Image of the Lumbar Spine
White MatterGrey Matter
dorsal
ventral
Coronal Image of the Lumbar Spine
caudalrostral
Sagital Image of the Lumbar Spine
dorsal
ventral
caudalrostral
Implanted Pl/Ir Wires
Transverse
Coronal
Sagittal
T2 Distributions
1 ms 1 s 10 s10 ms 100 ms
35 mm caudal
10 mm rostral
1 ms 1 s 10 s10 ms 100 ms
1 s
21 mm caudal
1 ms 1 s10 ms 100 ms 10 s
12 mm caudal
1 ms 10 ms 100 ms 10 s
white mattergrey matter
white matter sample region
grey matter sample region
Sample In-Vitro Spectrum
Lesion and Removal
The 24 rats injured with clip Complete laminectomy and spinal cords extracted at
4h, 24h, 1 week, or 4 weeks 6 control cords also extracted
Cords are cut into approximately 3 equal sections centered at T8
Sections are frozen in isopentane then liquid N2 and stored
at -80oC 800MHz (18.8T) 25oC sweep width = 12kHz 180o-τ-90o pulse and acquire 32 averages
CaudalLesion
Rostral
Choline Difference From Control
4 hour 1 day 1 week 4 weeks-0.01
0
0.01
0.02
0.03
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
±S
EM
*
CaudalLesionRostral
Glutamate Difference From Control
4 hour 1 day 1 week 4 weeks-0.06
-0.04
-0.02
0
0.02
0.04
0.06
0.08
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
±S
EM *
CaudalLesionRostral
Glutamine Difference From Control
Row 1 Row 2 Row 3 Row 40
2
4
6
8
10
12
Column 1
Column 2
Column 3
4 hour 1 day 1 week 4 weeks-0.1
-0.05
0
0.05
0.1
0.15
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
±S
EM
*
CaudalLesionRostral
Myo-Inositol Normalized to Central Control Section
Control 4 hour 1 day 1 week 4 weeks0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
No
rma
lize
d C
on
cen
tra
tion
±S
EM
**
CaudalLesionRostral
Myo-Inositol Difference From Control
4 hour 1 day 1 week 4 weeks-0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
±S
EM
**
*
*
CaudalLesionRostral
NAA Difference From Control
4 hour 1 day 1 week 4 weeks-0.15
0
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
±S
EM
*
**
*
*
CaudalLesionRostral
NAAG Normalized to Central Control Section
Control 4 hour 1 day 1 week 4 weeks0
0.2
0.4
0.6
0.8
1
1.2
No
rma
zed
Co
nce
ntr
atio
n ±
SE
MCaudalLesionRostral
**
NAAG Difference From Control CaudalLesionRostral
4 hour 1 day 1 week 4 weeks-0.06
-0.05
-0.04
-0.03
-0.02
-0.01
0
0.01
0.02
0.03
0.04
Diff
ere
nce
Fro
m C
on
tro
l (m
M)
± S
EM
*
*
*
**
*
*
In-Vivo MR Spectroscopy
Cr
Cho
ppm
NAA
3.5 3 2.5 3
Summary
Preoperative images with high detail can be obtained Distortion from Pl/Ir micro wires large enough to be
observed but small enough not to ruin the image. Water compartmentalization can separate mylin water from
other cellular water and this seems to change with injury Major changes are observable in-vitro in both Myline and
NAAG NAA, Creatine, and Choline can be observed in the spinal
cord in-vivo
Future Directions
Imaging of human spinal cord Imaging of Pl/Ir wires in a live cat Determining if water component ratios and times vary with
respect to time of injury Can Myo-Inositol or NAAG be observed in-vivo
Acknowledgments
Steve McGie Enid Pehowich Vivian Mushahwar Peter Allen Ryan McKay Chris Hanstock Brent McGrath