Magnetic resonance imaging and nuclear magnetic resonance ...
Magnetic resonance imaging in biomedical research
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Transcript of Magnetic resonance imaging in biomedical research
Magnetic resonance imaging in biomedical research
Igor Serša
Ljubljana, 2011
History of Nuclear Magnetic Resonance (NMR)
MultidimensionalNMR spectroscopy
Biomedcial use of NMR, magnetic resonance imaging (MRI)
1D NMR spectroscopy (CW)
NQR ,Solid state NMR,NMR in Eart‘s field
Emergence of computersPulsed NMR
R.R. Ernst (1975)
P.C. Lauterbur (1973)P. Mansfield (1973)
Purcell, Torrey, Pound (1946)Bloch, Hansen, Packard (1946)
Nobel Laureates in MRIR.R. Ernst 1991 chemistry
P. Mansfield 2003 medicine
P.C. Lauterbur 2003 medicine
For a discovery of multidimensional NMR and setting foundations of Fourier transform MRI methods
For the development of fast MRI (Echo planar imaging)
First who succeded to get a MR image
MRI in early days
Lauterbur, P.C. (1973). Nature 242, 190.
… and MRI now
MRI statistics
• MRI Equipment Market of 5.5 Billion Dollars in 2010
• 91.2 MRI exams are performed per 1,000 population per year in USA• 41.3 MRI exams are performed per 1,000 population per year in OECD countries• 22.2 MRI exams are performed per 1,000 population per year in Slovenia
• 7,950 MRI scanners in USA (25.9 MRI scanners per million population)• 18 MRI scanners in Slovenia (9 MRI scanners per million population)
Opening ceremony of the last MRI scanner in Slovenia (Murska Sobota)
Investment of 1,200,000 €
MRI systems
Clinical MRI systemUse in radiologyB0 = 1,5 T, opening 60 cm
High-reolution NMR/MRI system Use in chemistry, MR microscopyB0 = 7 T, opening 3 cm
Nuclear magnetization
m ii
pM
V
Nuclear precession
B0
RF pulseB1 field
100 MHz proton precession frequency in 2.35 T0 0B
1 pB t
M0/2
M0
tT1 ln(2)
Mz
MR signal
Ui
M
Ui
t
U0
FT
FID signal
spectrum
Magnetic field gradients
x
x
B0
B
x
Gx x+
=
Sedle coil Maxwell pair
MR imaging in one dimension
x xB B
0 0( )x 0( ) xx G x
MR imaging in two dimensions
back projection reconstruction method
Pulse sequencesRF
AQ
Gx
Gy
p/2 p
TE
Gz
MRI in biomedicine
Research on clinical MR scanners
Hardware development• RF coils• Gradient coils• Amplifiers• Spectrometers
Imaging sequences• Standard MRI• Contrast• Speed• Resolution• Spectroscopic
Data processing• New reconstruction algorithms• Image filtering• Mathematical modelling
Rsearch on other MRI systems
MR microscopy• MRI of wood• Pharmaceutical
studies• Porous materials• Biologoical Tissue
properties• MRI of food
Small anaimal MRI• Development of new MRI
contrast agents• Study of new drugs
Hardware developmentMulti channel RF coils(32 channel head coil)
Gradient amplifiers• Gradients up to 45 mT/m• Gradient rise time of 200 T/m/ms• 600 A @ 2000 V = 1.2 MW !
RF amplifiers• 35 kW MRI magnets
• 1.5 T, 3 T, 7 T• Low weight• Compact dimensions• Low helium consumption
Imaging sequencesType of sequence Principles Advantages Disadvantages Spin echo (SE) simple, SE
T1, T2, DP contrast Contrast Slow (especially in T2)
Multiecho SE SE several TE, several images DP + T2 images Slow, even if acquisition of the 2nd image does not lengthen acquisition
Fast SE SE, echo train effctive TE
Faster than simple SE simpleES contrast
Fat shown as a hypersignal
Ultrafast SE SE, long echo train, half-Fourier Even faster Low signal to noise ratio
IR RF 180°, TI + ES/ESR/EG T1 weighting Tissue suppression signal if TI is adapted to T1
Longer TR / acquisition time
STIR IR, short TI 150 ms Fat signal suppression Longer TR / acquisition time
FLAIR IR, long TI 2200 ms CSF signal suppression Longer TR / acquisition time
Gradient echo (GE) < 90° α and short TR No rephasing pulse
+ speed T2* not T2
GE with spoiled residual transverse magnetization
TR < T2 Gradients / RF dephasers
T1, DP weighting
Ultrafast GE small α and very short TR Gradients / RF dephasersk-space optimization
++ speedcardiac perfusion
Poor T1 weighting
Ultrafast GE with magnetization preparation
+ preparation pulse:- IR (T1weighted)- T2 sensibilization
++ speedAngioMRI GadoCardiac perfusion / viability
Steady state GE TR < T2 Rephasing gradients FID
+ signal++ speed
Complex contrast
Contrast enhanced steady state GE Rephasing gradientsHahn echo ( trueT2)
Not much signalT2 weighted
Balancedsteady state GE
Balanced gradients in all 3 directionsT2/T1contrast
++ signal, ++ speedFlow correction
Echoplanar Single GE or multi shotPreparation by SE (T2), GE (T2*), IR (T1), DWExacting for gradients
++++ speedPerfusionMRIf BOLDDiffusion
Limited resolution Artifacts
Hybrid echo Fast SE+ intermediary GE
++ speedSAR reduction
Clinical MR images
fMRI Fiber tracking MRI of spine
MR angiography DWI - stroke MRI – brain tumors
New reconstruction methods
R = 4
Sa’
Sb’= S
0 0 0 0
0 0 0 00 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
Sc’
Sd’
Small animal MRI
Experimental mice Anaesthesia Placement in the probe
const($$$)Resolution × SNRTime
SignalNoise
Resolution
Time
Multiple sclerosis model• Mice having Theiler’s Murine Encephalitis Virus infection (TMEV) may develop
symptoms similar to that of multiple sclerosis• Intracerebral injection causes demyelinating disease• CD8 cell mediated disease
Normal cord MS cord
T2-weighted imagesMS lesions (demyelinated choppy structures) appear bright
6 5 4 3 2 1 0ppm
7 days post infection
Before infection
NAA
CrCho
Decrease in NAA/Cr ratio in early stage of MS.
Superparamagnetic labells
Superparamagnetic antibodies under scanning electron microscope attached to CD8 cells.
• USPIO - Ultrasmall Super Paramagnetic Iron Oxide particle: 50 nm in diameter
• Highly specific superparamagnetically labeled antibodies: targeted USPIO-s
• Venous administration• Signal persists for days, excellent specificity• A single labeled cell can theoretically provide
adequate signal to be visualized
MS lesions detected by CD8 labeling
Day 0
Day 3
Day 7
Day 21
Day 45
B6 strain mice (acute demyelinating disease, full recovery in 4-6 weeks)
What is MR Microscopy?MR microscopy is essentially identical to conventional MRI (most of MR sequences of clinical MRI can be used) except that resolution is at least an order of magnitude higher.
1 mm / pixel
10-100 µm / pixel
Conventional MRI
MR microscopy
2D
3D
10 fold resolution increase
Signal -> Signal / 100
Signal -> Signal / 1000
How to compensate the signal loss?
• By using stronger magnets• By lowering the sample temperature (not an
option)• By signal averaging• By reducing RF coil size
7 – 14 T
20Signal B
RF coils in sizes from 2 mm – 25 mm
How to achieve high resolution?By the use of stronger gradients
45 mT/m @ 750 A
1500 mT/m @ 60 A
Conventional MRI
MR microscopy
Δt
GR
Δt
GR
2
R
FOVG tp
MRI laboratory at JSI100 MHz (proton frequency)2.35 THorizontal bore superconducting magnet
Accessories for MR microscopyTop gradients of 250 mT/m, RF probes 2-25 mm
Our research using MR microscopy
http://titan.ijs.si/MRI/index.html
Electric current density imaging NMR of porous materials MRI of wood
Volume selective excitation MRI in pharmaceutical research
NMR in studies of thrombolysis
MRI in dental research
NMR in studies of thrombolysis
pump
magnet
3 mm0,7 mm
30 mm
p = 15 kPa (113 mmHg), arterial system
p = 3 kPa (22 mmHg), venous system
blood clot
0,5 l plazma + rt-PA
3 mm
Flow regime v [m/s] Re
Fast flow
begining 4,26 1660
end 0,86 1430
Slowflow
begining 0,19 75
end 0,01 18
• ηk = 1.8·ηH20 = 0.0018 Pas• ρk = 1035 kg/m3
NMR in studies of thrombolysisTE = 12 msTR = 400 msSLTH = 2 mmFOV = 20 mmMatrix: 256 x 256
0 min 4 min 8 min 12 min 16 min
0 min 4 min 8 min 12 min 16 min
Slow flow
Fast flow
Dynamical 2D MR microscopy using spin-echo MRI sequence
NMR in studies of thrombolysis
1 /x S S
S∞
SS0S0
x1
t
T
0 500 1000 1500 2000 25000
0.2
0.4
0.6
0.8
1
Hiter tok
Počasen tok
t [s]
x
SERŠA, Igor, TRATAR, Gregor, MIKAC, Urška, BLINC, Aleš. A mathematical model for the dissolution of non-occlusive blood clots in fast tangential blood flow. Biorheology (Oxf.), 2007, vol. 44, p. 1-16.
Fast flow
Slow flow
NMR in studies of thrombolysis
• 3D RARE MRI (fast flow, ∆p = 15 kPa)
0 min 36 min
0 2 4 6 8 10 120,0
0,2
0,4
0,6
0,8
1,0
1,2
t = 36 min
chan
nel r
adius
R [m
m]
entrance length z [mm]0 2 4 6 8 10 12
0,0
0,2
0,4
0,6
0,8
1,0
1,2
chan
nel r
adius
R [m
m]
entrance length z [mm]
t = 0 min
NMR in studies of thrombolysis
2
( )r R
v v vdA Fds S dt S z dtr r r
• Blood clot dissolution progresses radially with regard to the perfusion channel along the clot.
• Volume blood flow through the clot is constant.• Mechanical forces to the surface of the clot have viscous origin and are
therefore proportional to the shear velocity of blood flow along the clot.
20 / ( )Vv Rp2R∞ 2R
λ
FConfocal microscopy of thrombolysis
5 μm
J. W. Weisel, Structure of fibrin: impact on clot stability, J Thromb Haemost 2007
• Mechanical work needed for the removal of the clot segment is proportional to its volume.
• Start of thrombolytic biochemical reactions is delayed (τ) and gradual (Δ)
NMR in studies of thrombolysis
dA cdV c S dR
1 1 1( ) 1 exp(( ) / )c t c t
τ
Δ
t
1/c∞
1/c
2R
dR
Layer of the clot that is well perfused with the thrombolytic agent
Layer of the clot that is removed in time dt
λ
NMR in studies of thrombolysis
1
7 7240
0 07
17 7
00
7
1 exp(( ) / )ln 1 1 ;1 exp( / )
( , )
1 exp(( ) / )ln ; .1 exp( / )
D
R tR z z z zTR
R z t t
R tR z zR T
7 24
7 00 0
7
7 00
ln exp 1 1 1 1 exp 1 ;
( )
ln exp 1 1 exp 1 ; .
D
T R z z z zR
t zT R
z zR
Perfussion channel profile
Thrombolytic time
SERŠA, Igor, VIDMAR, Jernej, GROBELNIK, Barbara, MIKAC, Urška, TRATAR, Gregor, BLINC, Aleš. Modelling the effect of laminar axially directed blood flow on the dissolution of non-occlusive blood clots. Phys. Med. Biol., 2007, vol. 52, p. 2969-2985.
NMR in studies of thrombolysis
Current density imaging
The aim of this study was to monitor current density during high-voltage electroporation (important for electrode design and positioning)
Externally applied electric field is used to induce cell permeability by transient or
permanent structural changes in membrane
Current density imaging
Electroporation phantom
Current density imaging
Effect of electric pulses
Current density imaging
Current encoding part
Imaging part
CDI calculation
yB
xB
xB
zB
zB
yBj xyzxyz
CDI ,,1
0
2. Ampere law
1. Phase is proportional to Bz
Thin-sample approximation
tyxByx zCDI ,,
0,,1
0 xB
yBj zzCDI
Electric pulses• Two 20 ms pulses @ 15 V• Eight 100 μs pulses @ 1000 V
Current density imaging
5 10 15 20 25 30
5
10
15
20
25
30
x y
Vector field (jx,jy)
2 4 6 8 10 12 14 16
2
4
6
8
10
12
14
16
51015202530
5
10
15
20
25
30
x
y Vector field (jx,jy)
246810121416
2
4
6
8
10
12
14
16
Phase image 2D current density field
experiment simulationElectrode setup
MRI of woodOn a 3m high beech tree, transplanted in a portable pot, a branch of 5mm diameter was topped. The topped branch was then inserted in the RF coil and then in the magnet.
MRI of wood
Pith, xylem rays, early wood vessels and cambial zone
6 mm 21 mm
MRI of wood• Trees do not have a mechanism to heal wounds like higher organisms
(animals, humans), i.e., wounds are not gradually replaced by the original tissue.
• In trees wounds are simply overgrown by the new tissue, while the wounded tissue slowly degrades.
Wound
Dehydration and dieback
Formation of the reaction zone
new grown tissues
MRI of wood
Day 8
Day 3
Day 1
MRI of wood
Day 28
Day 14
Day 168
MRI in dental research
root channel
bifurcation
enamel
dentin
pulp
periodontalcommunications
Premolars
1-2 root channels
Molars
3-4 root channels(in the literature was reported even up to 7 root channels)
MRI in dental research
• Standard X-ray image corresponds to 2D projection of hard dental tissues (enamel and dentin) into a plane of image.
• It is impossible to accurately determine the exact number of root channels since they may overlap in the projection.
• Fine details (periodontal communications and anastomosis) cannot be seen due to limited resolution.
• X-ray scanning is harmful due to X-ray radiation.
Root channels are not clearly visible.
Root channels after endodontic treatment.
MRI in dental research
X-ray imageHard dental tissues are bright on the images, soft tissues cannot be seen.
MR image obtained after co-addition of all slicesSoft dental tissues are bright on the images, hard tissues cannot be seen. Frontal (bucco-lingual) as well as side (mesio-distal) view is possible.
MRI in dental research
MRI in dental research
Conclusion
• MRI is very versatile.• Its applications range from clinical routine in
radiology to research in medicine, biology as well as in material science.
• Close collaboration between scientists and industrial engineers enabled an enormous development of MRI from an unreliable imaging modality to the new radiological standard.