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1. AMRIS Mission • Technology Development for High Field MRI/S »» Multi-frequency RF probe development »» HTS probe development »» MAS probe development »» Coils tailored for unique capabilities »» Microimaging at micron resolution »» Nanomaterials for multimodal imaging »» Mixture analysis • Unique Applications for High Field MRI/S »» A menagerie of animals (mouseelephant) »» Imaging at cellular resolution »»Diffusion on a nanometer to micron scale »» Low gamma detected MRI/S »» Biophysics and structural biology »» Chemical ecology and metabolomics »» Natural products

2. Transformative (NSF NHMFL; 350k/yr) Translational (NIH, non-NHMFL NSF, Private Foudations, DOE; 600k/yr and growing) • External User Program • Materials for Imaging in Extreme Environments • RF and technique development • Physical phenomena • Complex coordination of H2O • Contrast mechanisms • Accelerated acquisition techniques • Measuring and matching of magnetic susceptibility • Managing and measuring anisotropic interactions Human Imaging Animal imaging Molecular and Cellular Imaging Structural biology Complex mixture analysis Metabolomics Simple NMR Properties to Study Complex Biological Problems

3. Grant portfolio AMRIS supports (~$40M/yr; centers, program projects and individual investigator grants) National High Magnetic Field Laboratory Powell Gene Therapy Center Neuromuscular Diseases – Muscle Plasticity VA Brain Rehabilitation Research Center Center for Emotion and Attention Claude D. Pepper Older Americans Center Stem Cell Regeneration Initiatives Image Processing/ Computational analysis Nanotechnology Initiative Metabolomics Materials Characterization Structural Biology

4. Major Projects • Funded • Currently >80 federally funded projects (>$40M annually) utilize AMRIS • Two NIH program projects (P01) with imaging cores • Upgrade of 4.7 (NSF ARRA) and 11T consoles (NIH SIG); new animal imaging specialist • NIH R01 for 1.5-mm HTS probe to optimize both 1H and 13C S/N • New Agilent 600 MHz system for HTS probes/metabolomics (NIH R01; Chemistry) • Pending • NIH R01 for development of MR Microscopy at the cellular level (2nd percentile) • NIH R01 to track cellular migration in the heart via MRI (1st percentile) • NIH SIG to upgrade 600 MHz console (perfect score) • NIH U54 to study muscular dystrophies using novel contrast approaches is one of three anticipated funded centers in the country. • Helium recovery proposal with UF Physics, High B/T: NSF Academic Research Infrastructure Program: Recovery and Reinvestment (ARI-R2) • In our future • 3T upgrade to 32 channels and hire of PhD level human imaging specialist • Development of 36T SCH, DNP and HTS NMR user programs • AMRIS facility HVAC and layout renovation NIH ARRA Limited Competition: Core Facility Renovation, Repair, and Improvement (G20) received favorable score but not funded

5. Moving Forward Challenges for this upcoming year Hiring of RF staff and/or faculty (Barbara Beck is retiring) Upgrade of 500 MHz console (1-2 years) Hiring of PhD level staff scientist in human imaging Expansion of 3T to 32 channels/multi-transmit Long Term Outgrowing our space and meeting user demand 36T and DNP user programs Pursuit of HTS NMR program

6. 16' Mechanical Limited Animal Handling 4.7T/330 Animal Handling 11.7T/54 11.1T/400 c14.1T/54 17.6T/89 14.1T/54 X Current AMRIS wing Blue indicates non-laboratory space Red solid circles indicate 5G lines

7. Mechanical 4.7T/330 Animal Handling 22.3T/54 16.4T/54 11.7T/54 11.1T/400 7T/310 c14.1T/54 17.6T/89 14.1T/54 Liquid N2 Proposed AMRIS wing We could either add three conventional high field systems or an HTS magnet Cost of $1.5 M

8. NMR & MRI/S at 30T and above • Transformational research • Flow and diffusion over multiple length and timescales in deep structures • Bridging the gap between molecular and ultrastructural imaging • Characterization of complex systems • Challenges we need to address • Accelerated acquisition techniques • Measuring and matching of magnetic susceptibility • Managing and measuring anisotropic interactions • Development of contrast agents • Technical foci • Microimaging program (1-2 mm3 FOV at micron resolution) • NMR of biomolecular systems using microvolumes • Commercial partnering for consoles, cryogenics and LTS outserts

9. Current affiliated faculty Users Industry Technical development Applications -------------- -------------- -------------- -------------- -------------- -------------- -------------- -------------- ----------------------------- -------------- -------------- -------------- -------------- -------------- -------------- -------------- --------------- -------------- -------------- -------------- --------------- -------------- -------------- -------------- --------------- -------------- 5 5-6 Medicine Engineering Chemistry Physics in partnership with NHMFL Medicine Chemistry Health Professions >50

10. Proposed Growth Institution Service Infrastructure Industry Technical development Applications -------------- -------------- -------------- -------------- -------------- -------------- -------------- -------------- ----------------------------- -------------- -------------- -------------- -------------- -------------- -------------- -------------- --------------- -------------- -------------- -------------- --------------- -------------- -------------- --------------- -------------- --------------- -------------- -------------- --------------- -------------- -------------- -------------- --------------- -------------- -------------- -------------- --------------- -------------- -------------- --------------- --------------- CTSI NHMFL Medicine Engineering Chemistry Physics in partnership with NHMFL Medicine Chemistry Health Professions >50

11. Scientific Focus Signal detection in an extreme environment H2O, self assembly and hierarchical structures in biology and materials science Bridging atomic and anatomical scales in biology Systems biology and chemical communication Molecular medicine and personalized care Recommended Faculty Hires(State match to renewal?) Chief Scientist in Chemistry & Biology Biomolecular NMR (BMB or Chemistry) RF engineering (ECE or BME) Diffusivity and flow (BME or physics) fMRI (Aging or BRCC)

12. Science Highlights of the AMRIS MRI/S Program • First MRI microscopy of mammalian neurons and subcellular structures • Two cover articles in NeuroImage • Imaging with direct histological characterization of nucleoli in frog ova • Development of stronger gradients and perfusion probe with Bruker • High resolution brain white matter fiber structure • Fiber tract connections between major anatomical regions • Transport models for convection-enhanced CNS delivery • Natural product identification • ~1 mL of a “defensive ooze” from a leaf insect • We found 3 related pyrazines (smells like chocolate!) • Required the 1-mm HTS probe (right before it broke…) • Gene reporter for detection of cellular LacZ expression by MRI Pre Sgal Post Sgal -LacZ as of summer 2010, mid-point in current award period