Organisation und Infrastruktur der translationalen ... · Organisation und Infrastruktur der...
Transcript of Organisation und Infrastruktur der translationalen ... · Organisation und Infrastruktur der...
Mitg
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emei
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Organisation und Infrastrukturder translationalen Forschung am
FZ Jülich
N. Jon Shah, DirectorInstitute of Neurosci ence and Medicine – 4
Forschungszentrum Jülich GmbH52425 Jülich
Germany
Institute of Neuroscience and Medicine
Architektonicsand brain functionProf. Dr. K. Amunts
Structural und Functional
Organisation of the Brain
Prof. Dr. K. Amunts
Morphometryand image analysisProf. Dr. U. Pietrzyk
Cognitive NeurologyProf. Dr. G.R. Fink
Medical ImagingPhysics
Prof. Dr. N.J. Shah
MR PhysicsProf. Dr. N.J. Shah
PETProf. Dr. H. Herzog
Brain tumoursProf. Dr. K.-J. Langen
MolecularOrganisation of the Brain
Prof. Dr. K. Zilles
Transmitters-receptors
Prof. Dr. K. Zilles
Structureof Synapses
Prof. Dr. J. Lübke
MolecularNeuroimaging
Prof. Dr. A. Bauer
Functional neuronal circuits
Prof. Dr. D. Feldmeyer
System MedicineProf. Dr. Dr. P. A. Tass
NeurotechnologyPD Dr. C. Hauptmann
NeuromodulationProf. Dr. Dr. P. A. Tass
MathematicalNeuroscience
PD Dr. O.V. Popovych
Nuclear ChemistryProf. Dr. H.H. Coenen
RadionucleiDevelopmentDr. B. Scholten
Radio-pharmacology
Dr. D. Bier
RadiotracerDevelopment
Dr. D. Holschbach
RadiotracerProductionDr. J. Ermert
Dr. K. HamacherMEG
Prof. Dr. N.J. Shah
Analyse der Struktur und der funktionellenProzesse des Gehirns (organismischeEbene), der Nerven- und Sinneszellen(zelluläre Ebene) sowie der fürSignalübertragung relevanten Moleküle(molekulare Ebene),
um Organisationsprinzipien sowienormale und pathologisch veränderteMechanismen des Nervensystems zuverstehen, und
neue Diagnoseverfahren und Therapien fürneurologische und psychiatrischeErkrankungen zu entwickeln.
Forschungsziele
Hirnforschung an Gesunden und Kranken zur Analyse neurologischer und psychiatrischer Erkrankungen
Entwicklung neuer bildgebender Techniken und selektiver Radiotracer für das „Neuroimaging“ mit MRT, PET, SPECT und MEG, sowie fluoreszenzmarkierter Biomoleküle und anderer Verfahren für das „zelluläre Imaging“ und die biophysikalische Strukturanalyse
Entwicklung neuer Therapien wie z.B. bedarfsgesteuerte Tiefenhirnstimulation, elektrische oder chemische Neuromodulation
Forschungsprogramme und Methoden
Vom Radioisotop zur Hirndiagnose
Radionuklidproduktion
Radiotracerherstellung
Qualitätskontrolle/GMP
Pharmakologische Evaluierung
Anwendung beim Menschen
C11
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TCH 3
Teilchenbeschleuniger
Syntheseautomat
Radiochromatographie
In vitro Autoradiographie
PET-Aufnahme
Concept for Translational Research
Research/Clinical4T
Human
Clinical 3T
MRI-PET Human
Clinical 3T
Human
Clinical 1.5T
Human
9.4T MR Animal
9.4T MRI-PET
Human
RESEARCH
TransFOR
Research
Clinical
9.4T
Ani
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Sca
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in
Jülic
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3T MR-PET
3T MR-PET Scanner in Jülich
Res
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Sca
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Jül
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1.5
T3
T
4 T
Quantitative
Shah*Gras
Keil
Abbas
Lindemeyer
Sequences
StöckerKaffanke (50%)
Pflugfelder
Vahedipour
Brenner
Stirnberg
Diffusion
ShahMaximov
Grinberg
*Kupriyanova
Novel Contrasts
OrosPetersen
Kemper
Sodium
RomanzettiPracht
Fiege
9.4T MR-PET
Shah*Kaffanke
Kubach
*Ullisch
Hardware
FelderGeschewski
*Celik
Besançon
MRI
Imaging the Living Brain
Ultra High-Field MRI Quantitative Imaging (T1, T2*, Water, 23Na, 17O)
Animal Imaging (Home-built, Syngo-based 9.4T)
Brain Connectivity (DTI+fibre tracking as well as PLI)
Sodium Imaging Hybrid MR-PET (3T MR-PET, 9.4T MR-PET)
Molecular and Cellular PET Novel Tracers / Receptor (PET)
Neurodegeneration
MRI Highlights
Current MRI
Anatomy
Function
Temporal
Spatial
Development Prospects
Technological Maturity
Clinical Availability
Clinical Utility
Sensitivity/Specificity
Molecular Imaging
HighVery GoodGoodLowVery Low
Current PETAnatomy
Function
Temporal
Spatial
Development Prospects
Technological Maturity
Clinical Availability
Clinical Utility
Sensitivity/Specificity
Molecular Imaging
HighVery GoodGoodLowVery Low
Hybrid MR-PET
Anatomy
Function
Temporal
Spatial
Development Prospects
Technological Maturity
Clinical Availability
Clinical Utility
Sensitivity/Specificity
Molecular Imaging
HighVery GoodGoodLowVery Low
Localization and analysis of complex neuralmechanismsDomain of fMRI
Molecular level:
Neurotransmissiondriven by neurotransmitters and receptorsor modulated by drugsDomain of PET
Systemic level:Complex neuralfunctions
Hybrid-Imaging
Centers of cerebraldata processingDomain of fMRI
Biochemical Communication at the Synapse
modulated byinternal neurotransmitters or drugs
Domain of PET
Introduction
T1-MRI:morphology
86
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22
fmol/ml
33
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11C-Flumazenil-PET:benzodiazepine-receptors
Current commonly combined use of PET and MRI
Cerebral gliomas:PET with O-(2-[ 18F]fluoroethyl)-L-tyrosine (FET)completes MRI based diagnosis
Mismatch
Match
Preoperative determinationof tumor extent in FET-PET and MRI
MRI:Sensitivity: 96 %Specificity: 53 %
MRI+FET:93 %94 %
Pauleit et al. Brain 2005
Mul
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Industry - FZJ - BICW
NeurologyPsychiatry
A-B-C-D
9.4TMRI-PET
Neuro-Imaging
FZJ
Pharma
Biomed.
Mitglied der Helmholtz-Gemeinschaft
Hig
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igh-
Def
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nato
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In vivo anatomical imaging at 1.5T with 0.6mm 3 isotropic resolution
MP-RAGE, 10 separate scans coregistered and complex averaged off-line. Whole brain coverage. Shortest acquisition time: 3min:38s
In v
ivo
high
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olut
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anat
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(0.6
mm
3 ) a
t 1.5
T
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MR
I Seq
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opm
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MP-SAGE a new MRI sequence for high resolutionand high contrast human brain imaging
Stöcker T, Shah NJ. MP-SAGE: a New MP-RAGE Sequence with Enhanced SNR & CNR for Brain Imaging Utilising Square-Spiral Phase Encoding and Variable Flip Angles. Magnetic Resonance in Medicine 2006, Vol 56 (4):824-834.
Comparison to the standard approach (MP-RAGE)
MP-SAGEMP-RAGE
Imaging Brain Anatomy
A new theoretical description of the spin-dephasing for single-shot STEAM provides higher SNR:
High Field DTI
results at 4 Tesla
a) Standard single-shot STEAM measurement with a constant flip angle (α=20°)
b) Standard single-shot STEAM measurement with a variable flip angle approach (VFA)
c) New single-shot STEAM sequence with VFA for shaping a constant echo train
d) New single-shot STEAM sequence with an optimised VFA approach for an exponentially decaying echo train
e) Spin- Echo EPI image is strongly affected by susceptibility-induced artefacts.
Last column provides correct SNR comparison!
results at 4 Tesla:undistorted FA maps in sub-cortical brain regions
A new theoretical description of the spin-dephasing for single-shot STEAM provides higher SNR.
High Field DTI
Stöcker, Kaffanke, and Shah. Whole Brain Single-Shot STEAM DTI at 4 Tesla, Magnetic Resonance in Medicine, in revision
New results:parallel transmit / selective excitation
4 Tesla result:•8 Tx channel pseudo set up•3D selective excitation of a homogenous box
Simulation result:(JEMRIS)•8 Tx channels•3D checkerboard
Single channel:
Multi channel:
True 3D selective pulses:
•Solving a HUGE linear system•Using FZJ supercomputers•Examples below need 65 GB of RAM
Mitglied der Helmholtz-Gemeinschaft
Sod
ium
Imag
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at 4
T
in vivo sodium imaging of a healthy volunteer @ 4T
Conical SPRITE (acq time ~ 15min)
Romanzetti et al. 2006
in vivo sodium imaging of a healthy volunteer @ 4T
Conical SPRITE (acq time ~ 15min)
Romanzetti et al. 2006
ConclusionsConclusions
Need high fields 4T , 9.4T
SPRITE with efficient k-space trajectories and acquisition of multiple FID points
Sensitive to fast-decaying relaxation components
Clinical acquisition times feasible (~15min)
Direct quantitative measure of 23Na concentration
Conical-SPRITE is feasible in vivo
Conical SPRITE 5x5x10 mm3
voxel volume
Mitglied der Helmholtz-Gemeinschaft
Qua
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Imag
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Ena
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T
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Development of Quantitative MRI TAPIR (T1 mApping of Partial Inversion
Recovery) T2
* mapping Extension to mapping of water
How to do Translational Studies: an Example
Introduction
Measurement of T1 in vivo Detection of tissue abnormalities High in-plane resolution combined with
whole-brain coverage Quantitative VBM
Fast acquisition: reduction of image artefacts clinically useful
Implementation
TAPIR (T1 mApping of Partial Inversion Recovery)
Shah et al.,; US Patent No.: 6,803,762
Shah et al., NeuroImage: 2001 14(5): 1175-85
Steinhoff et al., Magn. Reson. Med.: 46(1) 131-140 2001
Zaitsev, et al; Magn. Reson. Med.: 49(1) 1121-1132 2003
Shah et al., Hepatology: 2003 38: 1219-26
Tapir: any perissodactyl mammal of the genus Tapirus …. of South and central America and SE Asia, having an elongated snout, three-toed hind legs, and four-toed forelegs.
500ms<T1<3s
Phantom Results
FLASH
Acquisition parameters:
TR=13ms; TE=1.9ms; TI=30ms; TD=3s; α=6°; 4 slices; 48 time points; 2562; FoV=250mm; slice-thickness = 8mm; interleaved
T1 Map
TAPIR: In vivo T1 Mapping
Large number of points affords reconstruction of accurate maps
Multi-exponential fitting is feasible
T1 mapping enables quantitative measurement of water content.
S(t) = M0 {1-2exp(t/T1)}
… life is not so simple!
Shah et al.,; US Patent No.: 6,803,762
Shah et al., NeuroImage: 2001 14(5): 1175-85
Steinhoff et al., Magn. Reson. Med.: 46(1) 131-140 2001
Zaitsev, et al; Magn. Reson. Med.: 49(1) 1121-1132 2003
Shah et al., Hepatology: 2003 38: 1219-26
1 4 7 12 35
Acquisition parameters:
TR=13ms; TE=1.9 / 2.7 / 3.5ms; TI=30ms; TD=3s; α=8°; 4 slices; 48 time points; 2562, FoV=230mm, slice-thickness = 5mm; interleaved
Typical T1 WM: 600 ±90ms
Typical T1 GM: 1000±25ms
TAPIR Results in vivo
Shah, Steinhoff, and Zaitsev; US Patent No: 6,8,762
Shah et al., NeuroImage: 2001 14(5): 1175-85
Steinhoff et al., Magn. Reson. Med.: 46(1) 131-140 2001
Zaitsev et al., Magn. Reson. Med.: 49(6) 1121-32 2003
Validation of TAPIR
Zatisev, Steinhoff, Zilles and Shah. Proc. ISMRM 2002
Representative in vivo T1 maps from 9-echo TAPIR
Mitglied der Helmholtz-Gemeinschaft
T2*
Map
ping
Man
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984
Spe
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PS
I)
Phantom and in vivo Results
Mitglied der Helmholtz-Gemeinschaft
Wat
er M
appi
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Water Content Mapping
Why? Normal Brain Water Content Highly Regulated
How? T1 Maps from TAPIR; T2
* Maps from QUTE
What is it good for? Oedema Monitoring of Therapy Voxel-Based Morphometry with Water Content
11/24/2009
50 60 70 80 90 100Phantom Water Content [%]
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MR
Measured
All CorrectionsNo RX SensitivityNo Flip Angle Correction
Tubes filled with different mixtures of (doped) normal water H2O and heavy water D2O. Heavy water is not MR visible at the proton resonance frequency!
Excellent agreement (<1.5%) between known mixing ratio and MR measured water content
Neeb et al., Intern. Congr. Series, 2004 Neeb et al., 13th ISMRM, 2005 Neeb et al., NeuroImage 2006 31 1156-1168
Water Content Mapping
Wat
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Gre
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Mat
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HE
I =
> H
E0
Neeb et al., Neuroimage 2006b 29 910-922
Water Content in Grey Matter
Neeb et al., 2006a,NeuroImage 31 1156-1168
Water Content in Grey/White MatterIn Controls
Neeb et al., Neuroimage 2006b 29 910-922
Age Dependence of H2O Content
Neeb, Zilles, and Shah. 2006, submitted
Water Content Mapping in vivo
Wat
er C
onte
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appi
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Tum
ours
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HepaticEncephalopathy
Measurement of the Effects ofManganese Depositionand Low-Grade CerebralOedema Non-Invasively
Shah et al., Hepatology: 2003 38: 1219-26Neeb H, Shah NJ. Magn Reson Med. 2006 56(1):224-9. Neeb H, Zilles K, Shah NJ. NeuroImage. 2006 31(3):1156-68. Neeb H, Zilles K, Shah NJ. NeuroImage. 2006 29(3):910-22.Shah et al., 2008 41(3):706-17
C5
Water Content Mapping @ 1.5T
Hepatic Encephalopathy grade HE 0
Shah et al., US Patent No.: 6,803,762Shah et al., NeuroImage: 2001 14(5): 1175-85Steinhoff et al., Magn. Reson. Med.: 46(1) 131-140 2001Zaitsev et al; Magn. Reson. Med.: 49(1) 1121-1132 2003Shah et al., German Patent No.: 10028171
Hepatic Encephalopathy grade HE II
putamen putamen
thalamus
White Matter Water Content in HE
Shah NJ et al., Neuroimage. 2008;41(3):706-17.
White Matter Water Content and Therapy
HE I => HE0
Shah NJ et al., Neuroimage. 2008;41(3):706-17.
11/24/2009
HE 0 HE II
Water Content Mapping @1.5T
Shah NJ et al., Neuroimage. 2008;41(3):706-17.
11/24/2009
White MatterCONTROL70.8±0.48
HE 071.1±0.44
SHE 71.6±0.45
HE I72.9±0.66
HE II72.8±0.17
(Mean±S.E.M.)
Water Content Mapping in HE
Shah NJ et al., Neuroimage. 2008;41(3):706-17.
11/24/2009
Significant correlation between HE grade and water content
• Frontal and Occipital WM
• Putamen
• Globus Pallidus
• Posterior Limb of the Internal Capsule
HE Grade vs. H2O content
Shah NJ et al., Neuroimage. 2008;41(3):706-17.
Mitglied der Helmholtz-Gemeinschaft
New
Dire
ctio
ns fo
r T
rans
latio
n:M
R-P
ET
at 3
T a
nd 9
.4T
MR instead of CT in PET/CT ?
M.Schwaiger, S.Ziegler, et al., 2005
The combination of MR and PET in one scanner allows the
simultaneous and complementary use of these modalities
Siemens
Avalanche photo diodes (APD)
vs. photo multiplier tubes (PMT)
PMT APDAPDPMT
insensitiveMagnetically sensitive
~5 ns~1 nsRisetime
Up to 200Up to 10 6Gain
5x5 mm10-52 mm dia.Size
Installed in Jülich in autumn 2008:MAGNETOM Trio with a BrainPET
30 min 18F-PET
SimultaneousT1 MPRAGE
Fusion
18F in Hoffman 3D brain phantom
Our first human MR-PET images
Brain tumour studied with 18F-fluoro-ethyl-tyrosine (FET)
Mitglied der Helmholtz-Gemeinschaft
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Conclusions
The MR-BrainPET allows simultaneous scanning!
Artefacts seen in the first images have been reduced
Qualitative PET imaging shows excellent resolution
Quantitative PET is to be achieved
9.4T MR scanner functional
Sodium single channel Tx, 8 channel Rx built
JEMTIS simulation environment demonstrated
Acknowledgments
Thanks to:
H. Herzog, L. Tellmann, B. Marx, E. Rota Kops, J. Scheins, and C. Weirich (Juelich)
K.J. Langen, G.Stoffels, J. Kaffanke (Juelich)
A. Oros, J. Felder, T. Stöcker, K. Vahedipour (Juelich)
L. Byars, C. Michel, M. Schmand, E. Rummert(Siemens, Knoxville)
J. Kampmeier, M. Fenchel (Siemens, Erlangen)
BMBF
Tha
nkyo
u
for
your
atte
ntio
n!!