multimodal functional mri (多模态功能磁共振成像)
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Sir Peter Mansfield Magne0c Resonance Centre
University of No:ngham, UK
FP7 Neurophysics Workshop Pharmacological fMRI
Warwick Conference Centre, 23 January 2012
Mul0modal approaches to func0onal neuroimaging
Peter Morris
Functional MRI
Functional CNR
ΔS/N = SNR . ΔR2* / R2*
7T MPRAGE, 0.5mm isotropic resolution, SENSE factor 2, acquisition time 11 mins for the whole head
1.5T
3T
7T
5 s-1
0.39 s-1
5 s-1
5 s-1
0.39 s-1
0.39 s-1
ΔR2* maps as a func0on of strength
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Composite ROI Inclusion ROI
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Composite ROI Inclusion ROI
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Composite ROI Inclusion ROI
Field dependence of ΔR2*/R2*
Field dependence of fMRI responses
pcorr < 0.05 for motor task
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TE (ms)
7 T3 T1.5 T
ΔS/S
Motor task (8 s ON; 20 s off; 5 cycles) Same 6 subjects scanned at 1.5, 3 & 7 T Data co-registered across fields and echo times.
W. van der Zwaag, S. Francis, K. E. Head, A. Peters, P. Gowland, P. Morris and R. Bowtell, Neuroimage 47, 1425-1434 (2009)
anterior
posterior
1-thumb 2-index 3-middle 4-ring 5-little
ventral
dorsal
right
High resolution somatosensory mapping at 7T
2
1
4 3
5
Relating structure to function in the visual cortex at 7T
medial lateral fMRI
Structural
Rotating wedge
V1
posterior anterior
structural
functional
1.5 mm isotropic resolution
Resolution:0.35x0.35x1.5mm3
Stria of Gennari
seen as a dark band
Resting state networks
J.R. Hale, M.J. Brookes, E.L. Hall, J.M. Zummer, C.M. Stevenson, S.T. Francis and P.G. Morris, Magn. Reson. Mater. Phy. 23, 339-349 (2010)
Correlation coefficients for sensorimotor and default mode resting state networks
J.R. Hale, M.J. Brookes, E.L. Hall, J.M. Zummer, C.M. Stevenson, S.T. Francis and P.G. Morris, Magn. Reson. Mater. Phy. 23, 339-349 (2010)
Default mode network
Sternberg Working Memory Task
Paradigm: Two visual stimuli presented in quick succession
Following a maintenance period of 8s, a third “probe” stimulus presented
Subject responds if the the probe is the same as either of the two initial stimuli
Visual Stimulus 1
Visual Stimulus 2
M a i n t e n a n c e P e r i o d
Probe Stimulus
Working Memory (Sternberg) Paradigm
S. Clare, M. Humberstone, J.L. Hykin, L.D. Blumhardt, R. Bowtell and P.G. Morris, Magn Reson Med 42, 1117-1122 (1999)
Challenges of pharmacological MRI
• Direct affect (BOLD response) of agent – DifferenCaCon between direct and acCvity mediated effects on haemodynamic response
– Pharmacodynamics
• Modulatory effect of agent – Pharmacodynamics
Rat Model of Persistent Nociception
Intraplantar injection of formalin into rat hindpaw
Ascending and descending pain pathways
hl fl
a
vpm
vpl
vl
PAG
Thalamus
Formalin evoked increase in BOLD response
P<0.05
P<0.01
P<0.001
Hindlimb area of Somatosensory
cortex
Thalamus Amygdala
PAG
P.G. Morris, J. Psychopharm. 13 (4), 330-336 (1999)
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salinemorphine
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salinemorphine
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hang
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% c
hang
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Periaqueductal gray Thalamus
An acute high dose of morphine (5mg/kg, IP
cannula) evoked significant increases (p<0.002) in
BOLD response in the PAG, thalamus and cingulate
cortex -0.5
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salinemorphine
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Cingulate cortex
Effects of morphine injection
MEG at the SPMMRC
w1
w2
w3
w275
m1
m2
m3
w1 m1 + w2 m2 + w3 m VE = 3+
m275
MEG beamformer
Vq=Σi=1..275wqimi
Σ
virtual electrode output
Stimulus was a rotating wedge containing a 10Hz
flashing checkerboard.
Wedge rotated through 360 degrees smoothly once
every 25 seconds.
Functional images created using adaptive beamformer
using short covariance windows
Functional images show the location of the 10Hz driven neuromagnetic response
Response is mapped retinotopically onto the
occipital cortex
Retinotopic mapping using MEG
M. J. Brookes, J. M. Zumer, C. M. Stevenson, J. R. Hale, G. R. Barnes, J. Vrba, and P. G. Morris, Neuroimage 49(1), 525-538 (2010)
MEG responses
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Hilbert Transform of VE timecourse from peak of gamma 60-80Hz Subj2
• Evoked response
• Gamma band ERS
• Beta band ERD and ERS
Multimodal imaging: fMRI / MEG
7T BOLD
T>6
fMRI
3T BOLD
T>5.5
MEG β-band ERS (15-30Hz) Ŧ>1.2
VEP Ŧ>5
γ-band ERS (60-80Hz) Ŧ>4
β-band ERD (15-30Hz) Ŧ>1.2
M.J. Brookes, A.M. Gibson, S.D. Hall, P.L. Furlong, G.R. Barnes, A. Hillebrand, K.D. Singh, I.E. Holliday, S.T. Francis, P.G. Morris, Neuroimage 26 (1), 302-308 (2005)
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Michelson Contrast
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MEG Contrast Response Curves
Correlation of fMRI BOLD with neural oscillations
J.M. Zumer, M.J. Brookes, C.M. Stevenson, S.T. Francis and P. G. Morris, Neuroimage 49(2) 1479-1489 (2010)
Working memory
1-BACK 0-BACK 2-BACK RELAX
A… H S S G V D P… X S S D V K D… H Y R D V D
TARGETS
Time (s) 0 32 64 96 126
Time (s)
LETTER PRESENTATION MAINTENANCE RELAX
A D Y C Y M S P
8s 8s 2, 5 or 8 letters: 1 letter presented
every 1.4s
C
1.4s 2s
REL
AX
PRO
BE
N-BACK
STERNBERG TARGET
N-back and Sternberg paradigms
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Number of Subjects
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e C
hang
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itive
Cha
nge
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ativ
e C
hang
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itive
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Theta (4-8 Hz) activity during N-back (upper) and Sternberg (lower) paradigms. Group effect.
Gamma (20-40 Hz) activity during N-back (upper) and Sternberg (lower) paradigms Group effect
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Number of Subjects
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ativ
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Number of Subjects
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Spectral changes in oscillatory power in medial frontal lobe:
N-back
Spectral changes in oscillatory power in medial frontal lobe:
Sternberg
M.J. Brookes, J.R. Wood, C.M. Stevenson, J.M. Zumer, T.P. White, P.F. Liddle and P.G. Morris, Neuroimage 55, 1804-1815 (2011)
ICA analysis of resting state data M.Brookes, M. Woolrich, H. Luckoo, D. Price, J.R. Hale, M.C. Stephenson, G.R. Barnes,
S.M. Smith and P.G. Morris, PNAS 108 (40), 16783-16788 (2011)
ICA analysis of resting state data M.Brookes, M. Woolrich, H. Luckoo, D. Price, J.R. Hale, M.C. Stephenson, G.R. Barnes,
S.M. Smith and P.G. Morris, PNAS 108 (40), 16783-16788 (2011)
Resting state networks: MEG
Resting state brain networks observable using both fMRI and MEG in the “resting state”
Shows that the haemodynamic networks in fMRI have an electrophysiological basis
MEG also shows that neural oscillatory processes underlies haemodynamic connectivity
Agrees with invasive measurements made in patients
Brookes et al. PNAS 108 (40): 16783-16788 (2011)
Networks associated with working memory tasks
A: Visual, B: Fronto-Parietal, C: L/R Insula, D L/R TPJ, E: R Motor, F: L Motor, G Lateral Visual, H: Medial Parietal
Sternberg Working Memory Task
Paradigm: Two visual stimuli presented in quick succession
Following a maintenance period of 8s, a third “probe” stimulus presented
Subject responds if the the probe is the same as either of the two initial stimuli
Visual Stimulus 1
Visual Stimulus 2
M a i n t e n a n c e P e r i o d
Probe Stimulus
Sternberg Working Memory Task
Primary visual areas
Lateral visual areas
Bilateral Insula network
Fronto-parietal network
Medial Parietal cortex
Bilateral TPJ
Right Motor Cortex
Left Motor Cortex
Time frequency plots for 8 networks associated with Sternberg paradigm
Pathways of Glu/Gln and GABA/Glu/Gln Cycling"
Gln
Glu
Gln
Glu
Glu
GABA Gln GABAc
GAD67
GAD65
Na+ Na+ GABA
Glutamatergic neuron GABAergic neuron Astrocyte
TCA Cycle
TCA Cycle
TCA Cycle
Brain Neurotransmission
Advantages of high field for MRS
• Increased SNR (~ B0) – improved spa0al resolu0on – shorter scan 0mes
• Increased spectral resolu0on • Simpler spin coupling paVerns
– weak rather than strong coupling
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• Click to edit Master text styles • Second level
• Third level • Fourth level • Fifth level
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1H MRS Repeatability: %CVs
NAA Glu Gln mI GABA Cr Cho 7T sh 3 (2) 4(2) 10(6) 9(3) 10(6) 3(2) 5(4) 3T sh 5(3) 8(6) 29(11) 8(4) 21(14) 10(4) 16(16)
7T long 6(6) 10(6) 29(19) 19(10) 16(8) 7(6) 8(6) 3T long 6(6) 16(9) 32(30) 22(10) 36(25) 22(13) 8(7)
Values are mean (± SD)
M. C. Stephenson, F. Gunner, A. Napolitano, P. L. Greenhaff, I. A .MacDonald, N. Saeed, W. Vennart, S. T. Francis and P. G. Morris, World J. Radiol. 3(4), 105-113 (2011)
7T 1H Spectrum
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• Third level • Fourth level • Fifth level
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The stimulus consists of radial white/black prisms covering the entire visual field and reversing at a frequency of 8Hz.
Visual Stimulus
SCmulaCon induced changes in metabolite levels determined by 1H MRS
Lin et al., under revision for JCBFM
Time courses of metabolite changes
during visual stimulation
Lin et al., under revision for JCBFM
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• Third level • Fourth level • Fifth level
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• Significant decrease in Glc – Increased glucose consumption during stimulation
• Significant increase in Lactate – Increased rates of glycolysis and TCA cycle
• Suppression of second lactate response to stimulation • Significant increase in Glutamate, decrease in Glutamine and trend
to increase in GABA - Changes in the neurotransmitter levels due to increased turnover
• Significant Increase in Glutathione – Possibly related to oxidative stress or a ‘buffer’ of excess
synaptic glutamate
1H MRS Changes due to Visual Stimulation
Acknowledgements
• All my colleagues at the Sir Peter Mansfield Magne0c Resonance Centre, and especially Sir Peter
• Wellcome Trust, MRC, EPSRC, MS Society & others for grant support