Igor Serša Ljubljana 2011 History of Nuclear Magnetic Resonance NMR Multidimensional NMR spectroscopy Biomedcial use of NMR magnetic resonance imaging MRI 1D NMR spectroscopy CW NQR ID: 225156
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Slide1
Magnetic resonance imaging in biomedical research
Igor
Serša
Ljubljana, 2011Slide2
History of Nuclear Magnetic Resonance (NMR)
Multidimensional
NMR spectroscopy
Biomedcial use of NMR, magnetic resonance imaging (MRI)
1D NMR spectroscopy (CW)
NQR ,
Solid state NMR,
NMR in Eart‘s field
Emergence of computers
Pulsed NMR
R.R. Ernst (1975)
P.C. Lauterbur (1973)
P. Mansfield (1973)
Purcell, Torrey, Pound (1946)
Bloch, Hansen, Packard (1946)Slide3
Nobel Laureates in MRI
R.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 imageSlide4
MRI in early
days
Lauterbur
, P.C. (1973).
Nature
242, 190.Slide5
… and MRI
nowSlide6
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
S
obota)Investment of 1,200,000 € Slide7
MRI systems
Clinical MRI system
Use in radiology
B
0
= 1,5 T, opening 60 cm
High-reolution NMR/MRI system
Use in chemistry, MR microscopy
B0 = 7 T, opening 3 cmSlide8
Nuclear magnetizationSlide9
Nuclear precession
B
0
RF
pulse
B
1
field
100 MHz proton precession frequency in 2.35 T
M
0
/2
M
0
t
T
1
ln
(2)
M
zSlide10
MR signal
U
i
M
w
U
i
t
U
0
FT
w
FID signal
spectrumSlide11
Magnetic field gradients
x
x
B
0
B
x
G
x
x
+
=
Sedle coil
Maxwell pairSlide12
MR imaging in one dimension
x
x
B
B
w
0
w
wSlide13
MR imaging in two dimensions
back projection reconstruction methodSlide14
Pulse sequences
RF
AQ
Gx
Gy
p/2
p
TE
GzSlide15
MRI in biomedicine
Research on clinical MR scanners
Hardware development
RF coils
Gradient coils
AmplifiersSpectrometers
Imaging sequences
Standard MRIContrast
SpeedResolutionSpectroscopic
Data processingNew reconstruction algorithms
Image filteringMathematical modelling
Rsearch on other MRI systems
MR microscopyMRI of woodPharmaceutical studies
Porous materialsBiologoical Tissue propertiesMRI of food
Small anaimal MRI
Development of new MRI contrast agentsStudy of new drugsSlide16
Hardware development
Multi 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 consumptionSlide17
Imaging sequences
Type 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 dephasers
k-space optimization
++ speed
cardiac perfusion
Poor T1 weighting
Ultrafast GE with magnetization preparation
+ preparation pulse:
- IR (T1weighted)
- T2 sensibilization
++ speed
AngioMRI
Gado
Cardiac perfusion / viability
Steady state GE
TR < T2
Rephasing
gradients
FID
+ signal
++ speed
Complex contrast
Contrast enhanced steady state GE
Rephasing gradients
Hahn echo ( trueT2)
Not much signal
T2 weighted
Balanced
steady state GE
Balanced gradients in all 3 directions
T2/T1contrast
++ signal, ++ speed
Flow 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 Slide18
Clinical MR images
fMRI
Fiber tracking
MRI of spine
MR angiography
DWI - stroke
MRI – brain tumorsSlide19
New reconstruction
methods
R
= 4
S
a
’
S
b
’
=
S
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
S
c
’
S
d
’Slide20
Small animal MRI
Experimental mice
Anaesthesia
Placement in the probe
const($$$)
Resolution × SNR
Time
Signal
Noise
Resolution
TimeSlide21
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 images
MS lesions (demyelinated choppy structures) appear bright
7 days post infection
Before infection
NAA
Cr
Cho
Decrease in NAA/Cr ratio in early stage of MS.Slide22
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 visualizedSlide23
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)Slide24
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
3
D
10 fold resolution increase
Signal -> Signal / 100
Signal -> Signal / 1000Slide25
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
RF coils in sizes from 2 mm – 25 mmSlide26
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
Δ
t
G
R
Δ
t
G
RSlide27
MRI laboratory at JSI
100 MHz (proton frequency)
2.35 T
Horizontal bore superconducting magnet
Accessories for MR microscopy
Top gradients of
250 mT
/m, RF probes 2-25 mmSlide28
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 researchSlide29
NMR in studies of thrombolysis
pump
magnet
3 mm
0,7 mm
30 mm
D
p
= 15 kPa (113 mmHg), arterial system
D
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
Slow
flow
begining
0,19
75
end
0,01
18
η
k
= 1.8·
η
H20
= 0.0018 Pas
ρ
k
= 1035 kg/m
3Slide30
NMR in studies of thrombolysis
TE
= 12 ms
TR
= 400 ms
SLTH = 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 sequenceSlide31
NMR in studies of thrombolysis
S
∞
S
S
0
S
0
x
1
t
T
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 flowSlide32
NMR in studies of thrombolysis
3D RARE MRI
(
fast flow,
∆
p
= 15 kPa)
0 min
36 minSlide33
NMR in studies of thrombolysis
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.
2
R
∞
2
R
λ
F
Confocal microscopy of thrombolysis
5
μ
m
J. W. Weisel, Structure of fibrin: impact on clot stability,
J Thromb Haemost
2007Slide34
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
τ
Δ
t
1/
c
∞
1/
c
2
R
dR
Layer of the clot that is well perfused with the thrombolytic agent
Layer of the clot that is removed in time
dt
λSlide35
NMR in studies of thrombolysis
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.Slide36
NMR in studies of thrombolysisSlide37
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 Slide38
Current density imaging
Electroporation phantomSlide39
Current density imaging
Effect of electric pulsesSlide40
Current density imaging
Current encoding
part
Imaging
part
CDI calculation
2. Ampere law
1. Phase is proportional to
B
z
Thin-sample approximation
Electric pulses
Two 20 ms pulses @ 15 V
Eight 100 μs pulses @ 1000 VSlide41
Current density imaging
Phase image
2D current density
fie
l
d
experiment
simulation
Electrode setupSlide42
MRI of
wood
On 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.Slide43
MRI of
wood
Pith, xylem rays, early wood vessels
and
cambial
zone
6 mm
21 mmSlide44
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 tissuesSlide45
MRI of
wood
Day 8
Day 3
Day 1Slide46
MRI of
wood
Day
28
Day 14
Day
168Slide47
MRI in dental research
root channel
bifurcation
enamel
dentin
pulp
periodontal
communications
Premolars
1-2 root channels
Molars
3-4 root channels
(in the literature was reported even up to 7 root channels)Slide48
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.Slide49
MRI in dental research
X-ray image
Hard dental tissues are bright on the images, soft tissues cannot be seen.
MR image
obtained after co-addition of all slices
Soft dental tissues are bright on the images, hard tissues cannot be seen. Frontal (
bucco
-lingual) as well as side (
mesio
-distal) view is possible.Slide50
MRI in dental researchSlide51
MRI in dental researchSlide52
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.