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Hyperpolarized MRI. MRSRL Study Group 10.26.07 Presented by: Maryam Etezadi-Amoli. 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

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hyperpolarized mri

Hyperpolarized MRI

MRSRL Study Group


Presented by: Maryam Etezadi-Amoli

  • 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
polarization basics
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+ > N- Net polarization exists

polarization basics4
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!

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

Mansson et al., 2006

hyperpolarization is a non equilibrium state
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

concentration matters
Concentration matters!
  • Can’t 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

imaging considerations
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
imaging considerations9
Imaging considerations
  • Pulse sequence design
    • Longitudinal magnetization can’t 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
imaging considerations10
Imaging considerations
  • Need hardware (coils) tuned to multiple frequencies
  • Gradient limitations due to lower γ
    • γC-13 is 4x smaller than γ H-1
    • Need strong gradients to get same resolution in a given time
    • Or need to increase TE/TR…
hyperpolarization methods
Hyperpolarization methods
  • Polarization increases with B0 and decreasing temperature
  • Can we use brute force?
optical pumping op
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)
spin exchange optical pumping seop
Spin exchange optical pumping (SEOP)
  • Can be used for any nonzero-spin noble gas
  • Use circularly polarized light (laser, λ=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
metastability exchange optical pumping meop
Metastability exchange optical pumping (MEOP)
  • Can only be used with He-3
  • No need for alkali metal
  • Use laser light (λ = 1083 nm) to polarize electron state
  • Polarized electron state polarizes the He-3 nucleus
  • Faster than SEOP (tens of seconds)
parahydrogen induced polarization phip
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
phip pasadena
  • A variation of PHIP
  • Parahydrogen And Synthesis Allows Dramatically Enhanced Nuclear Alignment
dynamic nuclear polarization dnp
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
  • 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

  • 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
commonly used isotopes
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 don’t cause electric or magnetic field gradients at nucleus
he 3 and xe 129
He-3 and Xe-129
  • He-3
    • Produced from nuclear decay of tritium
    • γ= 32.4 MHz/T
    • Polarize to 40%
    • Can breathe He/O2 mixture indefinitely
  • Xe-129
    • Recover from atmosphere and isotopically enrich
    • γ= 11.9 MHz/T
    • Polarize to 20%
    • Anesthetic, but soluble in blood and tissue
t1 and t2 values in vivo
T1 and T2 values (in vivo)

Fain et al. JMR 2007

Golman et al. 2003

hyperpolarized mri vs contrast enhanced mri
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
hyperpolarized mri vs pet and spect
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 don’t have
some applications
Some applications
  • Angiography (No background signal!)
  • Perfusion mapping
  • Molecular/metabolic imaging
    • UCSF: in-vivo C-13 pyruvate
  • Interventional applications
  • Low field scans
golman et al 2003
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
golman et al 200327
Golman et al. 2003…
  • C-13 images 1s (a) and 2s (b) after injection
  • Scan time = 0.24s per image
  • SNR = 275 (vena cava)
golman et al 200328
Golman et al. 2003…
  • Theoretically achievable SNR

c γP

  • c = concentration (M)
  • γ= gyromagnetic ratio (MHz/T)
  • P = polarization
application catheter tracking
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

application lung imaging
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.
application lung imaging32
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
application low field mri
Application: Low field MRI
  • 3.8 mT scanner
  • Allows upright imaging

Mair et al., MRM (2005)

application low field mri34
Application: Low field MRI
  • SEOP hyperpolarized He-3
  • 20-40% polarization (2-4 hours required)
  • (a) supine
  • (b) upright with arm raised

Mair et al., MRM (2005)

application low field mri35
Application: Low field MRI
  • 6.5 mT
  • SEOP He-3
  • Supine (left)
  • Upright (right)

Tsai et al., ISMRM 2007

  • 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

Ardenkjaer-Larsen JH et al. Increase in signal-to-noise ratio of > 10,000 times in liquid state NMR. PNAS 100:10158-10163 (2003).

Fain S et al. Functional lung imaging using hyperpolarized gas MRI. JMR 25:910-923 (2007).

Golman K et al. Molecular imaging with endogenous substances. PNAS 100:10435-10439 (2003).

Golman K et al. Molecular imaging using hyperpolarized C-13. British Journal of Radiology 76:S118-S127 (2003).

Kohler SJ et al. In vivo C-13 metabolic imaging at 3T with hyperpolarized C-1-pyruvate. MRM 58:65-69 (2007).

Mair RW et al. He-3 lung imaging in an open access, very low field human magnetic resonance imaging system. MRM 53:745-749 (2005).

Mansson S et al. C-13 imaging—a new diagnostic platform. Eur Radiology 16:57-67 (2006).

Moller H et al. MRI of the lungs using hyperpolarized noble gases. MRM 47:1029-1051 (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.