Rohit Bakshi, MD, FAAN

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The Neuroimaging Technology Revolution
Rohit Bakshi, MD, FAAN Associate Professor of
Neurology Radiology Director, Laboratory for
Neuroimaging Research MS Center, Brigham
Womens Hospital Harvard Medical School Boston,
MA, USA rbakshi_at_bwh.harvard.edu
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The quest to image the brain
1920s
1930s
1950s
1970-80s
1980-90s
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The Neuroimaging Technology Revolution

• Atrophy
• Diffusion imaging
• Spectroscopy
• Higher field imaging
• New contrast agents
• Spinal imaging

• Post-processing
• Myelin imaging
• Magnetization transfer
• Perfusion imaging
• Functional MRI
• Optic imaging

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The Neuroimaging Technology Revolution
Assessment of atrophy
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Natalizumab (Tysabri) and brain atrophy in RRMS
(n942)
Year 0-1
Year 1-2
0
-0.1
-0.24
Placebo (n315)
-0.43
-0.40
-0.2
Natalizumab (n627)
-0.56
change in BPF
-0.3
-0.4
p0.004
-0.5
p0.002
-0.6
Miller et al. Neurology 2007681390-1401
Affirm Study
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Add-on treatment to limit whole brain atrophy
(BPF change) in RRMS of patients for 80
power

• 20 reduction n1000 per arm
• 33 reduction n400 per arm

Al Lo et al.
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Gray vs. white matter atrophy in MS

• Normalized to ICV BPF, GMF, WMF
• High reproducibility

Sanfilipo et al., Neuroimage 200526106877
Sanfilipo et al., Neurology 200666685692
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Gray vs. white matter atrophy in MS
Normal controls (n18)
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p.002
MS (n41)
0.9
0.8
0.7
p.0001
0.6
Global brain fraction
0.5
0.4
p.052
0.3
0.2
0.1
0
Whole brain (BPF)
Gray matter
White matter
Sanfilipo et al., Neuroimage 200526106877
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MRI correlation with disability

• Regression analysis GM the only predictor of
• EDSS (partial r .46, p.004)
• T25FW (partial r .52, p.002)

Sanfilipo et al., Neuroimage 200526106877
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Disease duration vs. gray matter volumeMS (n35)
Left lateral view
Right lateral view
Bakshi et al., unpublished data
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Caudate atrophy in MS 3-D MRI parcellation
MS
NL
Bermel et al., NeuroReport 200314335-339
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Thalamic atrophy related to cognition in MS
r 0.658, p lt 0.0001 (SDMT)
r 0.724, p lt 0.0001 (BVMT)
Houtchens et al., Neurology 2007691213-23
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The Neuroimaging Technology Revolution
Diffusion imaging
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Diffusion MRI

• provides information about the random motion of
  water molecules in vivo.

• In the white matter water diffusion is greater in
  the direction parallel to axons ? diffusion
  anisotropy

Alan Thompson et al.
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Fiber Tracking- Visualization of WM Tracts by DTI
Stanford DT Toolbox
T. Sherbondy, et al.Stanford
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Lesions and white matter tract damage diffusion
MRI
Dr. Daniel Goldberg
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The Neuroimaging Technology Revolution
MR Spectroscopy
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Normal MRS
Myoinositol-Choline-Creatine-Glutamine/glutamate-N
-acetyl aspartate-Lipids/lactate
ppm
4
3
2
1
0
The voxel localized on FLAIR image using
single-voxel point resolved selective
spectroscopy (PRESS) technique (TR 1500, TE of 35)
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Glatiramer Acetate (Copaxone) MRS of NAWM in RRMS
NAA/Cr
Khan et al. ECTRIMS. Multiple Sclerosis
200612(Suppl 1)S39
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Evidence for oxidative stress in MS measured
using MR spectroscopy at 7T Decreased Glutathione
glutathione maps
Daniel Pelletier et al. work in progress
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The Neuroimaging Technology Revolution
Higher field imaging
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MS brain hyperintensities 1.5T vs. 3T
2D FLAIR
2D FLAIR
1.5T
3T
Bakshi et al., Lancet Neurology 20087615-625
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MS Brain Atrophy 1.5T vs. 3T
SPGR
SPGR
1.5T
3T
Bakshi et al., Lancet Neurology 20087615-625
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FLAIR
Cortical Lesions in MS
T2WI
Bakshi et al., Arch Neurol, 200158742
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Multiple Sclerosis MRI at 8 T Cortical Gray
Matter Plaques
Kottil Rommohan et al.
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MS Cortical lesions Neuropathology
Immumocytochemical myelin stain, Bars200um
Type I WM Cortex
Type II Cortex, perivascular
Type III Pial/subpial
Peterson et al., Ann Neurol 200150389400
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MS Cortical lesions Neuropathology
Orangecortical plaque GreenWM plaque
Bluedeep GM plaque
Kutzelnigg et al., Brain 200512827052712
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MRI of brain iron

• T2 shortening (hypointensity)
• Susceptibility effect (T2 shortening)
• Advances with higher field strength

Perls stain
T2-SE at 4.0-T
Drayer and Schenck
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MRI Relaxometry Studies at 3T in MS
T2 Map
R2 Map
T2 Map
R2 Map
MS
Normal
TR 1500 msec Voxel size 0.9375 x 0.9375 x 2
mm
TR 2200 msec Voxel size 0.9375 x 0.9375 x 2 mm

• work in progress

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Iron a therapeutic window?

• Metal chelators
• Desferrioxamine, Dexrazoxane, Deferiprone,
  Triapine
• Free radical scavengers
• Edaravone, CI-186, Idebenone, Tempol
• Antioxidants
• Vitamin C, Vitamin E, Lazaroids

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200 ?m 200 ?m
38 y/o gentleman with 1 year of MS and EDSS score
of 1.0
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Nodular lesions Scattered lesions Ring lesions
34 y/o lady with 4 year of MS and EDSS score of
4.5
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Higher field MRI Challenges

• Hardware Footprint (weight/size), cost, coils
• Pulse sequence adaptation/development
• Inhomogeneity, susceptibility, chemical shift
• Patient comfort/safety
• Scanning time requirement
• Higher ambient noise
• RF deposition limits heating
• Sensory stimulation vertigo, pain
• Cardiac changes
• Implant compatibility

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The Neuroimaging Technology Revolution
New contrast agents
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MRI-USPIO in MSMonocyte/macrophage detection

• 33 USPIO lesions in 9/10 patients (31 Gd)
• 24 Gad lesions in 7/10 patients were USPIO-

T1-Gad
T2
T1-USPIO
Dousset et al., AJNR 200627100005
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MR Imaging of Myeloperoxidase (MPO)

• Enzyme secreted in inflammation by activated
  neutrophils, monocytes, and macrophages

Diffuse MPO
Demyelination
Macrophages/ microglia
Chen et al., Brain 20081311123-33
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The Neuroimaging Technology Revolution
Spinal cord imaging
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Whole spinal cord volume
Intra-rater, Inter-rater, Scan-rescan COV
0.2-0.6
work in progress
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Detecting MS Spinal Cord Lesions 1.5T vs. 3T
FSE T2 - 1.5T
FSE T2 - 3T
Stankiewicz et al. J Neurol Sci 2009 27999-105
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Proton MR Spectroscopy of Spinal Cord
Spinal cord

• Single voxel, PRESS
• Short TE
• Cardiac gating
• Scan time20 min
• Limitation
• Fat contamination
• CSF spinal cord motion
• Low SNR
• small size of cord

Voxel size 2.17ml
Cho Cr
NAA
Ins
Ciccarelli et al., Brain 20071302220-2231
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Diffusion tensor MRI of the spinal cord
Trace
Anisotropy directions
EDSS vs. (cord FA brain MD) r0.73 plt0.001
Valsasina et al., Neuroimage 2005
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The Neuroimaging Technology Revolution
Post-processing
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Subtraction Imaging
Follow-up
Subtraction
Baseline
Duan et al., AJNR 200829340-6
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T1-Gd
PD
T2w
Meier and Guttmann, Neuroimage 2003201193-1209
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Conclusion

• MRI technology continues to unfold in an almost
  limitless way
• A wider array of MRI tools are becoming available
  to assess the MS disease process
• Much validation and technical refinement yet to
  be done
• We can be thrilled as we imagine where the
  imaging field will go in the future

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Dream big!
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The Neuroimaging Technology Revolution
Rohit Bakshi, MD, FAAN Associate Professor of
Neurology Radiology Director, Laboratory for
Neuroimaging Research MS Center, Brigham
Womens Hospital Harvard Medical School Boston,
MA, USA rbakshi_at_bwh.harvard.edu