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National resource for high-field NMR imaging and spectroscopy

MBI-UF Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility. National resource for high-field NMR imaging and spectroscopy Focus on advanced basic and clinical applications and technology development

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National resource for high-field NMR imaging and spectroscopy

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  1. MBI-UF Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility • National resource for high-field NMR imaging and spectroscopy • Focus on advanced basic and clinical applications and technology development • “Biological-biomedical arm” of National High Magnetic Field Lab (NHMFL) http://www.mbi.ufl.edu/facilities/amris

  2. MBI-UF AMRIS Instrumentation • 136 Mhz, 3.0 Tesla, 60 cm horizontal bore • MRI/S of live animals (humans, primates, dogs, etc.) • 136 Mhz, 3.0 tesla, 80 ( 94) cm horizontal bore • MRI/S of live humans • 200 Mhz, 4.7 tesla, 33 cm horizontal bore • MRI/S of live animals (cats, rabbits, rats, mice, etc.) • 473 Mhz, 11.1 tesla, 40 cm horizontal bore • MRI/S of live animals (primates, cats, rabbits, rats, mice, etc.) • Solution state NMR spectroscopy of biomolecules (multiple samples) • 500 Mhz, 11.7 tesla, 5.2 cm vertical bore • Solution/solid state NMR spectroscopy of biomolecules • 600 Mhz, 14.1 tesla, 5.2 cm vertical bore • Solution state NMR spectroscopy of biomolecules • Cryoprobe to boost S/N by a factor of 4 • MRI/S of superfused cells/tissues • 750 Mhz, 17.6 tesla, 8.9 cm vertical bore • MRI/S of superfused cells/tissues & of live animals (e.g., mice) • Solution/solid state NMR spectroscopy of biomolecules (multiple samples) • Cryoprobe under development

  3. MBI-UF AMRIS: From Molecules to Man Single cell MRI/NMR High-Resolution Structural Biology Microsample (1.5ml) spectroscopy MR Microscopy (ex vivo) Animal MRI/MRS Human research

  4. c o i l C t MBI-UF AMRIS RF Engineering Lab Microcoils and arrays (MRI & MRS/NMR) Superconducting probes Phased array coils Human coils Large volume/High frequency Beck et al. (2002) MAGMA 13: 152-157

  5. MBI-UF AMRIS: 2002 User Research Highlights Brian Shilton (Univ of Western Ontario), Hargrave, Smith, McDowell, and Edison, “High-field structural studies of Rhodopsin/Arrestin complexes” Elisar Barbar (Ohio University) and Edison, “Structural biology of microtubule transport” Cottrell (St. Andrews), Zachariah, Dossey, Edison, “3D structure of a neuropeptide bound to its receptor” Webb (Illinois), Thelwall, Grant, Blackband, “NMR Microscopy of a Single Neuron Isolated from Aplysia Californica” Grant, Plant, Mareci, Blackband, Webb (Univ. Illinois), Aken (Univ. Arizona), “Proton Spectra from a Single Neuron Isolated from Aplysia Californica” Benveniste (Brookhaven Nat. Lab), Zhang (Brookhaven), Grant, Blackband, “MR Microimaging Studies of Mouse Brains For Generation of a Web Based Atlas and Methods for Identification of Brain Structures” Silver, Plant, Blackband, Benveniste (Brookhaven Nat. Lab), “Normal Mouse Brain MRI In Situ” Webb (Illinois), Zhang (Illinois), Edison, “Double Protein NMR coil”

  6. Funding for AMRIS provided by:

  7. Thank Dr. Stephen Blackband for providing the slices above

  8. High Field MR Technology Development Yu LI McKnight Brain Institute Advance Magnetic Resonance Imaging and Spectroscopy Facilities University of Florida, Gainesville, FL 32610

  9. Outline • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  10. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  11. History

  12. MR Research Areas • MR Spectroscopy • Solution state • Solid state • MR Imaging • Human/Animal imaging • Microimaging • Material imaging • Data Processing • Spectral data processing • Image reconstruction • Image post-processing

  13. High Field MR Technology • NIH Resource • Resource Cores: • High Field Small Animal Imaging • Microimaging and Microspectroscopy • High-sensitivity and High-throughput Solution State NMR

  14. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  15. MR Phenomena: Resonance B0 B0 Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http://www.EMBL-Heidelberg.de/nmr/

  16. MR Phenomena: Free Relaxation z M Mz  y Mxy x y x

  17. MR Signal: FID

  18. Nuclei of MR Interest

  19. MR Application Fourier Transform Image Reconstruction Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http://www.EMBL-Heidelberg.de/nmr/

  20. MR Instrumentation Magnet RF coil and Object Gradient coil Gradient coil Receiver Transmitter ADC Synthesizer Console

  21. Advantage: Information Rich • Molecule structure • Anatomical structure • Physiological mechanism • Pathophysiologies • Biological functional structure

  22. Drawback: Low SNR • Spectroscopy • Low sample efficiency • Low throughput • Imaging • Long imaging time • Low resolution High Field Technology

  23. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  24. Protein Structure Chain structure Amino Acid Primary Secondary Tertiary Quaternary

  25. Protein NMR Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http://www.EMBL-Heidelberg.de/nmr/

  26. Structure Information Frequency shift • Frequency shift: chemical structure dependence • Spectral peak structure: connection between different chemical groups

  27. Small Volume / High Field • Significance of small volume • Time of sample preparation • Expense • Availability • High field rationale B0 field RF coil design D.I.Hoult and R.E.Richards, J.Magn.Reson, 24, 71-85 (1976)

  28. Current Probe Technology Required sample volume: 600 µL

  29. Saddle and Solenoid Saddle Solenoid B1 Current: i Current: i “the disappointing signal-to-noise ratio experienced with superconducting system is a direct consequence of the use of saddle-shaped coils” D.I.Hoult and R.E.Richards, J.Magn.Reson, 24, 71-85 (1976)

  30. Solenoid Coil L2 C6 C5 C1 L4 C8 C4 L3 L1 C7 C2 C3 C12 C13 C10 C9 L5 1H C11 15N 13C C15 C14 Lock Solenoid Probe Design

  31. Experimental Comparison

  32. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  33. MR Parameters in Frequency Domain Fourier Transform Intensity Linewidth Frequency

  34. CE NMR SNR = 22.0 SNR = 36.6 Se(f) Seb(f) B(f) Noise

  35. Problem Formulation Srb(f) Sr(f) B(f) Noise Know Sr(f), Detect Srb(f), Estimate B(f) Seb(f) Se(f) B(f) Noise Know B(f), Detect Seb(f), Estimate Se(f)

  36. Gradient Decent Method es(f) eb(f) _ Se(f) _ B(f) B(f) Sr(f) + + Seb(f) Srb(f) (•)2 (•)2

  37. Gradient Decent Method Error function Parameters Optimum Values

  38. Multiresolution detection with wavelet High resolution / High SNR Low resolution / Low SNR Wavelet transform Scale decrease S. Mallat, and W.L. Hwang, IEEE Trans. on Information Theory, Vol. 38(2), 617-643 (1992).

  39. Resolving Results 100 mM sucrose in D2O

  40. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • MR Parameters Estimation • Imaging Technology • Summary

  41. MR Signal Intensity

  42. Image Contrast: MR Parameters-weighted • Proton density • Physical composition • T1 • Soft tissue • T2 • Tissue structure • Tissue metabolism • Pathophysiologies

  43. Image Contrast: MR Parameters-weighted • T2* • Vascular physiology • Biological functions • Apparent Diffusion Coefficient (ADC) • Tissue microstructure • Tissue composition • Tissue constitutes • Architectural organization

  44. 3D Brain / Spinal Cord Imaging T2-weighted Images of rat brain and spinal cord High resolution: below 40 µm (17.6T) B. Beck, D.H. Plant, S.C. Grant, PlE. Thelwall, X. Silver, T.H. Mareci, H. Benveniste, M. Smith, S. Crozier, S.J. Blackband

  45. Brain Slice Imaging Diffusion weighted microimage of rat brain slice High Resolution: 20 µm (14.1 T) S.J. Balckband, J.D. Bui, D.L. Buckley, T. Zelles, H.D. Plant, B.A. Inglis, M.I. Phillips

  46. Neuron Cell Imaging Diffusion-weighted images of a single neuron cell Cytoplasm (C) and nuclear (N) in artificial sea water (S). High Resolution: 20 µm (14.1 T) S.C. Grant, D.L. Buckley, S. Gibbs, A.G. Webb, and S.J. Balckband

  47. Roadmap • Research Background • Basic MR Principles • Small-Volume Protein NMR • Spectral Resolution Restoration • Imaging Technology • Summary

  48. High Field MR Technology • Hardware development • Magnet • Coil geometry / dimension • RF circuit design • Algorithm development • MR parameters estimation • Biomedical information and MR parameters • Image processing • EM field calculation

  49. Acknowledgement Jim Roca Paul Moliter William Brey Feng Lin Peter Gor’kov Jim Norcross Terry Green Drs Arthur Edison Andrew Webb Stephen Blackband Samuel Grant

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