MBIUF Advanced Magnetic Resonance Imaging and Spectroscopy AMRIS
MBI-UF Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility National resource for highfield 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
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
MBI-UF AMRIS: From Molecules to Man Single cell MRI/NMR High-Resolution Structural Microsample (1. 5 ml) spectroscopy Biology MR Microscopy (ex vivo) Animal MRI/MRS Human research
MBI-UF AMRIS RF Engineering Lab coil Ct Microcoils and arrays (MRI & MRS/NMR) Phased array coils Large volume/High frequency Beck et al. (2002) MAGMA 13: 152 -157 Superconducting probes Human coils
MBI-UF AMRIS: 2002 User Research Highlights Brian Shilton (Univ of Western Ontario), Hargrave, Smith, Mc. Dowell, 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, “ 3 D 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”
Funding for AMRIS provided by:
Thank Dr. Stephen Blackband for providing the slices above
High Field MR Technology Development Yu LI Mc. Knight Brain Institute Advance Magnetic Resonance Imaging and Spectroscopy Facilities University of Florida, Gainesville, FL 32610
Outline u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
History 1946 MR phenomenon – Bloch & Purcell 1952 Nobel Prize/Physics – Block & Purcell 1955 NOE Effect – Solomon 1966 Fourier transform NMR – Ernst, Anderson 1973 Backprojection MRI – Lauterbur 1975 2 D NMR – Jeener, Ernst; Fourier Imaging – Ernst 1980 MRI demonstrated – Edelstein 1985 Solution structure of small protein – Wüthrich 1986 Gradient echo imaging; NMR microscope 1987/8 3 D NMR + 13 C, 15 N isotope labeling 1989 Echo-planar imaging 1991 Nobel Prize/Chemistry – Ernst 1996/7 NMR development in maromolecular structure determination; Anisotropic diffustion 2002 Nobel prize/Chemistry – Wüthrich
MR Research Areas u MR Spectroscopy – Solution state – Solid state u MR Imaging – Human/Animal imaging – Microimaging – Material imaging u Data Processing – Spectral data processing – Image reconstruction – Image post-processing
High Field MR Technology u NIH Resource u Resource Cores: – High Field Small Animal Imaging – Microimaging and Microspectroscopy – High-sensitivity and High-throughput Solution State NMR
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
MR Phenomena: Resonance B 0 Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http: //www. EMBL-Heidelberg. de/nmr/
MR Phenomena: Free Relaxation z Mz M y Mxy x
MR Signal: FID MR Parameters i Factors Microrscopic environment Ai Nucleus spin density and Object volume Physiological or physicochemical properties Molecule mobility Ti i MR Signal Frequency shift Intensity
Nuclei of MR Interest Nuclei Net Spin (MHz/T) 1 H 1/2 42. 58 2 H 1 6. 54 31 P 1/2 17. 25 23 Na 3/2 11. 27 14 N 1 3. 08 13 C 1/2 10. 71 19 F 1/2 40. 08
MR Application Fourier Transform Image Reconstruction Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http: //www. EMBL-Heidelberg. de/nmr/
MR Instrumentation RF coil and Object Gradient coil Magnet Receiver Transmitter ADC Synthesizer Console
Advantage: Information Rich u Molecule structure u Anatomical structure u Physiological mechanism u Pathophysiologies u Biological functional structure
Drawback: Low SNR u Spectroscopy – Low sample efficiency – Low throughput u Imaging – Long imaging time – Low resolution High Field Technology
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
Protein Structure Amino Acid Chain structure Primary Secondary Tertiary Quaternary
Protein NMR Michael Sattler EMBL Heidelberg, Biomolecular NMR Structure, http: //www. EMBL-Heidelberg. de/nmr/
Structure Information Frequency shift u u Frequency shift: chemical structure dependence Spectral peak structure: connection between different chemical groups
Small Volume / High Field u Significance of small volume – Time of sample preparation – Expense – Availability u High field rationale B 0 field RF coil design D. I. Hoult and R. E. Richards, J. Magn. Reson, 24, 71 -85 (1976)
Current Probe Technology Required sample volume: 600 µL
Saddle and Solenoid Saddle Solenoid B 1 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)
Solenoid Probe Design Solenoid Coil L 2 C 6 C 5 C 1 L 1 C 4 C 2 L 4 L 3 C 8 C 7 C 3 C 12 C 9 1 H C 13 C 10 L 5 15 N C 14 Lock C 11 C 15 13 C
Experimental Comparison Solenoid Probe Sample Volume SNR 60 µL Commercial Saddle Probe 600 µL 97 91
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
MR Parameters in Frequency Domain Fourier Transform Intensity Linewidth Frequency
CE NMR SNR = 22. 0 SNR = 36. 6 Se(f) Seb(f) B(f) Noise
Problem Formulation Sr(f) Srb(f) B(f) Noise Know Sr(f), Detect Srb(f), Estimate B(f) Seb(f) B(f) Noise Know B(f), Detect Seb(f), Estimate Se(f)
Gradient Decent Method Sr(f) B(f) eb(f) _ B(f) + Se(f) es(f) _ + Seb(f) Srb(f) ( • )2
Gradient Decent Method Error function Optimum Values Parameters
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).
Resolving Results 100 m. M sucrose in D 2 O
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u MR Parameters Estimation u Imaging Technology u Summary
MR Signal Intensity MR Parameters Ai Factors Proton density Ti Physiological or physicochemical environment Molecule mobility i
Image Contrast: MR Parameters-weighted u Proton density – Physical composition u T 1 – Soft tissue u T 2 – Tissue structure – Tissue metabolism – Pathophysiologies
Image Contrast: MR Parameters-weighted u T 2* – Vascular physiology – Biological functions u Apparent Diffusion Coefficient (ADC) – – Tissue microstructure Tissue composition Tissue constitutes Architectural organization
3 D Brain / Spinal Cord Imaging T 2 -weighted Images of rat brain and spinal cord High resolution: below 40 µm (17. 6 T) B. Beck, D. H. Plant, S. C. Grant, Pl. E. Thelwall, X. Silver, T. H. Mareci, H. Benveniste, M. Smith, S. Crozier, S. J. Blackband
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
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
Roadmap u Research Background u Basic MR Principles u Small-Volume Protein NMR u Spectral Resolution Restoration u Imaging Technology u Summary
High Field MR Technology u Hardware development – Magnet – Coil geometry / dimension – RF circuit design u Algorithm development – – MR parameters estimation Biomedical information and MR parameters Image processing EM field calculation
Acknowledgement Drs Arthur Edison Andrew Webb Stephen Blackband Samuel Grant Jim Roca Paul Moliter William Brey Feng Lin Peter Gor’kov Jim Norcross Terry Green
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