Hyperpolarized MRI

1
Hyperpolarized MRI

• MRSRL Study Group
• 10.26.07
• Presented by Maryam Etezadi-Amoli

2
Overview

• Background and motivation
• Imaging considerations
• Hyperpolarization methods
• Optical pumping (OP)
• Para-hydrogen induced polarization (PHIP)
• Dynamic nuclear polarization (DNP)
• C-13, He-3, Xe-129
• Applications

3
Polarization basics

• Polarization (P) of spin 1/2 system

N spins parallel to B0 (low energy) N- spins
anti-parallel to B0 (high energy) N gt N- ? Net
polarization exists
4
Polarization basics

• Thermal equilibrium polarization

• P 5 x 10-6 for H-1 at 1.5T
• Even smaller for other species!
• There is room for orders of magnitude of
  improvement!

5
Hyperpolarization

• A non-equilibrium state where (N - N-) is
  increased by orders of magnitude compared to
  thermal equilibrium

Mansson et al., 2006
6
Hyperpolarization is a non-equilibrium state

• The resulting polarization value is independent
  of B0
• But this polarization has a limited lifetime
• Polarization will return to thermal equilibrium
  level at rate governed by T1

7
Concentration matters!

• Cant just look at polarization value
• Also need to consider the concentration of nuclei
• H-1 80M in biological tissues
• Hyperpolarized C-13 0.5M injected, decreases to
  1mM due to vascular dilution
• Any hyperpolarization scheme needs to give you
  enough polarization to make it worthwhile,
  considering other system losses

8
Imaging considerations

• Hyperpolarized magnetization is non-equilibrium
  and therefore not renewable
• Polarization is decaying to thermal equilibrium
  value at rate T1
• After each excitation pulse, longitudinal
  magnetization will recover to thermal equilibrium
  value, not hyperpolarized value

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Imaging considerations

• Pulse sequence design
• Longitudinal magnetization cant be recovered
• Each tip uses some hyperpolarization completely
• Pulse sequence design strategies
• Rapid train of low flip angle pulses
• Vary the flip angle to compensate for T1 decay
• Single shot imaging
• SSFP, trueFISP to recycle transverse magnetization

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Imaging considerations

• Need hardware (coils) tuned to multiple
  frequencies
• Gradient limitations due to lower ?
• ? C-13 is 4x smaller than ? H-1
• Need strong gradients to get same resolution in a
  given time
• Or need to increase TE/TR

11
Hyperpolarization methods

• Polarization increases with B0 and decreasing
  temperature
• Can we use brute force?

12
Optical pumping (OP)

• Used for noble gas isotopes He-3 and Xe-129
• Transfer angular momentum from circularly
  polarized light to gas nucleus
• Two methods
• Spin exchange (SEOP)
• Metastability exchange (MEOP)

13
Spin exchange optical pumping (SEOP)

• Can be used for any nonzero-spin noble gas
• Use circularly polarized light (laser, ?794.8
  nm) to polarize the valence electron shell of
  alkali metal Rb
• Energy from collisions of Rb atoms with noble gas
  atoms causes hyperpolarization
• Done in low B field (1-3 mT)
• Time required several hours

14
Metastability exchange optical pumping (MEOP)

• Can only be used with He-3
• No need for alkali metal
• Use laser light (? 1083 nm) to polarize
  electron state
• Polarized electron state polarizes the He-3
  nucleus
• Faster than SEOP (tens of seconds)

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Parahydrogen induced polarization (PHIP)

• Parahydrogen state where hydrogen nuclei are
  oriented such that magnetic moments cancel
• PHIP process
• Hydrogenate substrate containing C-13 with
  para-H2
• Use diabatic field cycling to convert
  non-equilibrium spin order of para-H2 to
  polarization of C-13 nucleus

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PHIP (PASADENA)

• A variation of PHIP
• PASADENA
• Parahydrogen And Synthesis Allows Dramatically
  Enhanced Nuclear Alignment

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Dynamic Nuclear Polarization (DNP)

• At low temp (1K) and high field (3T), electrons
  are highly polarized
• DNP transfers this polarization from the
  electrons to the C-13 nucleus
• Applies to nuclei other than C-13

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DNP

• Dope C-13 material with unpaired electrons
• Radiation near electron resonance frequency (94
  GHz) transfers polarization from electrons to
  C-13 nucleus

Golman et al., 2003
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DNP

• Need to rapidly dissolve the hyperpolarized solid
  to create a liquid, without losing the
  hyperpolarization
• Ardenkjaer-Larsen et al. (2003)
• C-13, 37 polarization
• N-15, 7.8 polarization

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Commonly used isotopes

• C-13
• Can construct many biologically relevant organic
  compounds (pyruvate, urea, lactate, alanine,)
• Noble gas isotopes He-3, Xe-129
• Spin 1/2
• Have long T1 since electrons from filled orbital
  shell dont cause electric or magnetic field
  gradients at nucleus

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He-3 and Xe-129

• He-3
• Produced from nuclear decay of tritium
• ? 32.4 MHz/T
• Polarize to 40
• Can breathe He/O2 mixture indefinitely
• Xe-129
• Recover from atmosphere and isotopically enrich
• ? 11.9 MHz/T
• Polarize to 20
• Anesthetic, but soluble in blood and tissue

22
T1 and T2 values (in vivo)
T1 (s) T2 (s)
He-3 (lung) 32 2-3
Xe-129 (lung) 30 0.31
C-13 urea 20 ?
Fain et al. JMR 2007
Golman et al. 2003
23
Hyperpolarized MRI vs. contrast enhanced MRI

• Hyperpolarized MRI differs from contrast-enhanced
  MRI
• Hyperpolarized agent acts as source of signal,
  rather than just modulating signal from protons

24
Hyperpolarized MRI vs. PET and SPECT

• Hyperpolarized MRI is similar to PET and SPECT
• Signal is proportional to concentration of agent
• But have the added advantage of spectroscopic
  information
• RF emitted by nuclei is sensitive to chemical
  environment
• Get molecular specificity that PET/SPECT dont
  have

25
Some applications

• Angiography (No background signal!)
• Perfusion mapping
• Molecular/metabolic imaging
• UCSF in-vivo C-13 pyruvate
• Interventional applications
• Low field scans

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Golman et al. 2003

• Imaged DNP hyperpolarized C-13 urea in
  anaesthetized rats
• 2.35 T animal scanner
• Measured T1 (in vivo) 20s
• Polarization at time of injection 10
• Compared with contrast enhanced H-1 angiography

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Golman et al. 2003

• C-13 images 1s (a) and 2s (b) after injection
• Scan time 0.24s per image
• SNR 275 (vena cava)

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Golman et al. 2003

• Theoretically achievable SNR
• c ? P
• c concentration (M)
• ? gyromagnetic ratio (MHz/T)
• P polarization

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Golman et al. 2003
H-1, 3T C-13 Urea C-13 Urea (ideal)
c (M) 80 0.1 1.0
? (MHz/T) 42.5 10.7 10.7
P 10-5 0.1 0.5
c ? P 0.034 0.11 3.2
Improvement over H-1 -- 3.2 100
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Application Catheter Tracking

• C-13 catheter tracking in pig aorta
• Frame rate 2 projections/second
• Images merged with 3D H-1 image

Mansson et al., 2006
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Application Lung imaging

• Lung is difficult to study with conventional H-1
  imaging
• Low H-1 density
• High air-tissue susceptibility difference at
  alveoli
• He-3 and Xe-129 hyperpolarized MRI
• Maps of ventilation/perfusion ratio
• Able to see lung defects related to asthma, COPD,
  cystic fibrosis.

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Application Lung Imaging
Moller et al., 2002

• He-3 of guinea pig lung, 1995
• b) He-3 of rat lung, 2002. Arrow points to
  airway 100um in diameter

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Application Low field MRI

• Mair et al., MRM (2005)

• 3.8 mT scanner
• Allows upright imaging

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Application Low field MRI

• Mair et al., MRM (2005)

• SEOP hyperpolarized He-3
• 20-40 polarization (2-4 hours required)
• (a) supine
• (b) upright with arm raised

35
Application Low field MRI
Tsai et al., ISMRM 2007

• 6.5 mT
• SEOP He-3
• Supine (left)
• Upright (right)

36
Conclusion

• Numerous applications exist, including molecular
  imaging of metabolically relevant nuclei
• Need to consider non-equilibrium state and effect
  on imaging requirements
• A way to supplement information from H-1 imaging

37
References

• Ardenkjaer-Larsen JH et al. Increase in
  signal-to-noise ratio of gt 10,000 times in liquid
  state NMR. PNAS 10010158-10163 (2003).
• Fain S et al. Functional lung imaging using
  hyperpolarized gas MRI. JMR 25910-923 (2007).
• Golman K et al. Molecular imaging with
  endogenous substances. PNAS 10010435-10439
  (2003).
• Golman K et al. Molecular imaging using
  hyperpolarized C-13. British Journal of
  Radiology 76S118-S127 (2003).
• Kohler SJ et al. In vivo C-13 metabolic imaging
  at 3T with hyperpolarized C-1-pyruvate. MRM
  5865-69 (2007).
• Mair RW et al. He-3 lung imaging in an open
  access, very low field human magnetic resonance
  imaging system. MRM 53745-749 (2005).
• Mansson S et al. C-13 imaginga new diagnostic
  platform. Eur Radiology 1657-67 (2006).
• Moller H et al. MRI of the lungs using
  hyperpolarized noble gases. MRM 471029-1051
  (2002).
• Tsai LL et al. Human lung imaging in supine
  versus upright positions with a 6.5 mT
  open-access He-3 MRI system Initial results.
  ISMRM 2007.