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Hyperpolarized MRI

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

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  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+ > 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! • 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

  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

  9. 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

  10. 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…

  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, 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

  14. 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)

  15. 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

  16. PHIP (PASADENA) • A variation of PHIP • PASADENA: • Parahydrogen And Synthesis Allows Dramatically Enhanced Nuclear Alignment

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. T1 and T2 values (in vivo) 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 don’t have

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

  26. 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

  27. Golman et al. 2003… • C-13 images 1s (a) and 2s (b) after injection • Scan time = 0.24s per image • SNR = 275 (vena cava)

  28. Golman et al. 2003… • Theoretically achievable SNR c γP • c = concentration (M) • γ= gyromagnetic ratio (MHz/T) • P = polarization

  29. Golman et al. 2003…

  30. 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

  31. 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.

  32. 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

  33. Application: Low field MRI • 3.8 mT scanner • Allows upright imaging Mair et al., MRM (2005)

  34. 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)

  35. Application: Low field MRI • 6.5 mT • SEOP He-3 • Supine (left) • Upright (right) Tsai et al., ISMRM 2007

  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 > 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.

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