Unsolved Problems and Unmet Needs in Magnetic Resonance

Unsolved Problems and Unmet Needs in Magnetic Resonance Morning Categorical Course ISMRM 14 th Scientific Meeting & Exhibition Seattle, WA, USA May 9 -12, 2005

Why a course on UNsolved problems? • At the annual ISMRM meeting and in many of our professional interactions, we tend to focus on what we or others have recently accomplished in our areas of interest, or else we speculate together on current trends and promising future directions in MR research and practice.

Why a course on UNsolved problems? • In the midst of all this lively and topical activity, the less satisfying questions of what we cannot but would very much like to achieve with MR receive little concentrated, collective attention.

Why a course on UNsolved problems? • Discussions of unmet needs and research priorities are often left to funding organizations, which publish periodic “requests for proposals” and “roadmaps” to which many of us as researchers are encouraged to respond. • The process of assessing needs and formulating priorities, however, could very well benefit from broader participation by our MR community at large.

Overview • The morning sessions on Unsolved Problems and Unmet Needs in MR are intended to bring new attention to such questions. • Over the course of the next four days, the top ten reviewed submissions from a prior call for abstracts on key problems and needs will be presented. • The sessions will also include substantial time for open discussion, in order to promote interactions and to foster innovation.

Educational objectives Upon completion of this session, participants should be able to: • Identify and assess a sampling of key unsolved problems and unmet needs in the field of magnetic resonance; • Establish criteria for successful solutions to such problems; • Consider any large-scale coordination across our field or with other fields that may be called for to address some classes of research or clinical needs; • Identify and share additional unsolved problems or unmet needs in your areas of interest.

Broader objectives: The ISMRM Strategic Plan • Vision: The ISMRM aspires to be the premier international society working to promote innovation, development, implementation, and communication of magnetic resonance science in medicine and other related fields.

Broader objectives • • Foster conversation (Strategic plan, goal 1) Foster collaboration (Strategic plan, goal 1) Foster innovation (Strategic plan, goal 1) Promote interactions between our clincially-focused and our research-focused members (goal 1) • Educate new entrants into our field (goal 2) • Develop a shared sense of collective targets for research (goals 1, 5, 6) • Play an active role in informing funding organizations by highlighting important directions (goals 1, 5, 6)

Precedents in other fields • Mathematics – Millennium Prize Problems, Clay Mathematics Institute (http: //www. claymath. org/millennium) – Multiple individual lists of unsolved problems: Hilbert, Croft, et al • Physics, Astronomy – Decadal Survey of Physics – Decadal Survey of Astronomy and Astrophysics (http: //www 7. nationalacademies. org/bpa/) • Medicine – The NIH Roadmap • Others – The National Academies Keck Futures Initiative Conferences (http: //www. keckfutures. org) – Intellectual Ventures, Nathan Myhrvold et al (http: //www. intellectualventures. com)

What do we mean by unsolved problems and unmet needs? • “If only I had X, then I could diagnose / monitor / treat Y” • “If only I could measure / build / control Z, then I could accomplish X” • “What is the true mechanism underlying Q? ” • …

What do you mean by unsolved problems and unmet needs? • Survey of ISMRM Study Groups returned nearly 100 items representing 7 Study Groups

MR Engineering 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Wireless or optical transmission of the MR signal out of the bore, to facilitate the use of large receiver coil arrays. What number of channels is optimal/required for both receive (Parallel Imaging) and transmit (Transmit SENSE) SAR: how to control SAR at high fields (> 3 T), how to know where the hot spots are in vivo, how to monitor the SAR in the human body in real time. Length of magnet/bore: how short can it be? What are the limits in openness? Actively shielded > 7 T whole body magnets. Dynamic shimming: development of shim coils that can be used in dynamic shimming (strong, low inductance, actively shielded) and quantification of the advantages to be gained via dynamic shimming. Reduction of acoustic noise to due switched magnetic field gradients, especially at high field. Methods for imaging without the use of pulsed field gradients. Methods for Precise QA of the MRI scanner in terms of SNR/ stability/ distortion/ artifacts and differences between MR methods. Currently, the lack of such methods limit the pooled use of MR data generated from different scanners/vendors. Practical methods for measuring the electrical properties of tissues using MRI. Methods for increasing patient throughput - can we produce an order-of-magnitude improvement in any way (parallel imaging, higher field, dockable tables, etc. ) in the time needed to image (leading to a reduction in scanning costs). A discussion board to draw an active group of engineers together for dissemination of knowledge and experience, rather than retainment in individual labs.

High-Field 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Solutions for the transmit B 1 inhomogeneity at high field due to wavelength/dielectric effects. Development of standardized method for SAR monitoring and setting SAR limits for multiple local transmit coils. Development of transmit SENSE at ultra-high field, along with development of algorithms for determining the phase and amplitude of the RF for each driven element in a coil, such as a TEM coil. Acoustic noise reduction at high field. Low noise, high fidelity, and powerful gradient amplifiers. Development of an actively shielded 7 T whole-body sized magnet. Fast CSI pulse sequences. Pulse sequences for clinical applications of hetero-nucleus imaging (such as 3 Li, 31 P, 17 O, etc. ) Detection of molecular probes that can pass through the blood-brain barrier and selectively bind to specific cells or tissues. A method for identifying areal boundaries via high resolution MRI (to allow definition of functional areas on individual subjects). Long-term health consequences of exposure to very high magnetic field. Methods to remove magnetic susceptibility-induced image distortion.

Diffusion/Perfusion 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. “Definitively quantify the contributions of the intra- and extra-cellular components to the diffusion signal “Measure brain perfusion in acute stroke patients accurately enough to be useful” [Score = 27; Number of votes = 7] “Have realistic phantoms for diffusion imaging” [Score = 26; Number of votes = 11] ”Quantify connectivity between different regions, separated by different distances, reliably and consistently” [Score = 25; Number of votes = 8] “Have an accepted and practical gold standard for tract tracing in the human brain” [Score = 23; Number of votes = 7] “Reliably measure the vascular territories of individual arteries” [Score = 21; Number of votes = 6] “Better understand the biophysical nature of diffusion MR signal, in order to optimize diffusion experiments more effectively” [Score = 20; Number of votes = 4] “Have a definitive, reproducible and easy way of calibrating ASL experiments with respect to M 0 (of tissue or blood, depending on the model) in order to get quantitative CBF values” [Score = 18; Number of votes = 4] “Use diffusion-derived measures, other than the mean diffusivity, in a clinical manner” [Score = 16; Number of votes = 5] “Have standard post-processing software (including motion correction) for ASL integrated onto a clinical scanner” [Score = 16; Number of votes = 5] “Perform meaningful group comparisons on low dimensionality diffusion data (scalar invariants of the tensor), even if we don’t understand the biophysical mechanisms underlying them” / “Perform meaningful voxel-based comparisons of DTI data” [Score = 16; Number of votes = 4] “Reliably quantify the dependence of diffusion on diffusion time, to identify different tissue types or geometrical features” [Score = 15; Number of votes = 5] “Have realistic phantoms for perfusion imaging” [Score = 15; Number of votes = 5] “Use DTI to reliably discriminate tumor infiltration from bland ( tumorfree) edema” [Score = 14; Number of votes = 5] “Use arterial spin labeling to measure perfusion in white matter” [Score = 14; Number of votes = 3] "Establish the definitive biophysical mechanism underlying the dependence of ADC on the b-value in the brain". [Score = 12; Number of votes = 4] “Resolve the topological ambiguity in diffusion displacement profiles (cross, kiss, twist, bend)” [Score = 11; Number of votes = 4] “Reach a common consensus, once and for all, on the number of directions needed for DTI, and the b-values needed (i. e. , do we need b < 600 s/mm 2 or b> 3000 s/mm 2)” [Score = 11; Number of votes = 4] “Identify the cellular correlates of changes in diffusion anisotropy in white matter” [Score = 11; Number of votes = 5] “Know whether FA abnormalities in specific fibers correlate with f. MRI abnormalities in gray matter (i. e. , use DTI to predict the outcome of f. MRI experiments)” / “Identify the functional basis and the functional meaning of DTI” [Score = 10; Number of votes = 5

MSK 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Applications of Parallel Imaging in MSK MRI New coils for 3 T and 7 T: phased array, small coils Kinematic and loaded imaging of joints and spine Novel sequences to image cartilage including SSFP and u. TE Automated segmentation and parameter mapping software (morphology, T 1, T 2, T 1 rho) Spectroscopy for MSK MRI - muscle, spine, cartilage (1 H, 31 P, Na) Fat saturation for low field - robust Dixon imaging New hardware: gradient inserts and dedicated extremity 3 T systems Fast T 1 and T 1 rho mapping sequences DWI and DTI imaging for muscle and nerves 11. Marrow Imaging

Flow and Motion 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. How to achieve robust, accurate, high-temporal-and-spatial-resolution flow measurements in, for example, the right and circumflex coronary arteries, which move a lot. We need a well-defined, complex flow phantom for comparison/calibration of scanners. How to have first-time, every-time measurements of flow with likely errors less than 10% in PATIENTS in vessels down to 5 mm diameter? What consistutes a clinical report of an MR flow study? an MR cardiac motion study? When will MR velocimetry match ultrasound? Spiral, EPI, segmented gradient echo, FVI, etc, do we have the right tools for every situation? and do we really need them all in clinic and in research settings? Limits of temporal, spatial and velocity resolution - how low and how high can we go (in flow and tagging)? How well does phase mapping work with accelerated imaging techniques? How do I know if a flow study was done well? 4 D velocity mapping - how fast? how good?

Dynamic MR 1. 2. 3. 4. A hand-held MRI scanner. The NMR mouse exists and is capable of measuring spectra at very small depths. However, for hand held medical imaging we would need to a. Create a reasonably homogeneous B 0 field penetrating the body to organ depth. b. Overcome B 0 field inhomogeneities. c. Create reasonably linear B 0 gradients d. Compensate for the residual non-linearity of the gradients. e. Have MRI sequences with only adiabatic pulses f. Have enough B 1 penetration for the adiabatic pulse without exceeding SAR limits. Create “The mother of all sequences” (so named by Paul Bottomley), a truly high resolution 3 D pulse sequence that in a reasonably short scan time measures spin density, T 1 and T 2. Then use this information to generate any slice at any oblique angle with any T 1 or T 2 weighted contrast. This would replace the series of scout images, oblique scouts, T 1 and T 2 weighted images that usually make examinations long. Measure real time changes in spin density at a time scale shorter than T 1. Example measure real time changes in phosphorous metabolites or in intracellular sodium in vivo in muscle or other excitable tissue. Measure changes in T 1 at a time scale shorter than T 1. White Matter 1. 2. 3. 4. 5. 6. How to distinguish between demyelination, inflammation and axonal loss? Early diagnosis of Alzheimers (before occurrence of atrophy) Increased specificity for diagnosis of Multiple Sclerosis in patient with WM lesions Possibility to establish glioma grading with high confidelity Expand the MRI capabilities for brain white matter to high resolution imaging of the spine columns Diagnose White Matter Pathology Definitively using MRI.

This year’s initiative: Abstract review • Each abstract reviewed by at least 3 referees (AMPC members, with expertise chosen to match the abstract topics) • Abstracts graded separately from regular ISMRM abstracts, but on a similar point system • The ten top-rated submissions selected for oral presentation, and grouped into themes

This year’s initiative: Topics over the week • Tue May 9: What are we missing? Seeing through metal and divining with RF coils • Wed May 10: Can MRI provide a noninvasive biopsy? • Thu May 11: Will new contrast agents revolutionize MRI? • Fri May 12: Do we need a virtual scanner, and do we understand real ones?

Tuesday • What are we missing? Seeing through metal and divining with RF coils • Moderators: Stuart Crozier, Michael Smith • 07: 00: Introduction Daniel K. Sodickson, M. D. , Ph. D. • 07: 15: Techniques for MR Imaging Near Metallic Implants Garry E. Gold, M. D. • 07: 30: Prospects of Absolute B 1 Calibration Florian Wiesinger, Ph. D. • 07: 45: Open Discussion

Wednesday • Can MRI provide a noninvasive biopsy? • Moderators: Michael Moseley, John Detre • 07: 00: Cytoarchitectonic MRI: Can MRI Be Used to Quantify Neural Tissue? Itamar Ronen, Ph. D. • 07: 15: Tissue Structure through Diffusion and Transverse Relaxation Measurements Valerij G. Kiselev, Ph. D. • 07: 30: Unresolved Issues in Diffusion and Perfusion MRI: A Consensus from the Study Group Derek K. Jones, Ph. D. • 07: 45: Open Discussion

Thursday • Will new contrast agents revolutionize MRI? • Moderator: Thomas Grist, Martin Prince • 07: 00: Exclusively MRI - Based Molecular Imaging: Can Magnetic Labeling of Physiologically Important Compounds via DNP or Parahydrogen-Induced Hyperpolarization Provide a Potential Supplement or Replacement of PET? Joachim Bargon, M. D. • 07: 15: Direct Detection of Neuromodulation Rachel Katz-Brull, Ph. D. • 07: 30: Development of Status Tracers for Myocardial Perfusion Imaging by MRI Timothy F. Christian, M. D. • 07: 45: Open Discussion

Friday • Do we need a virtual scanner, and do we understand real ones? • Moderators: David Hoult, Richard Bowtell • 07: 00: Need for a Non-Commercial Open-Source MR Simulator • 07: 15: Ralf B. Loeffler, Ph. D. Does the Principle of Reciprocity Hold at High Field MR? Jinghua Wang, Ph. D. • 07: 30: Reciprocity at High Field: Counterpoint David Hoult, Ph. D. • 07: 40: • 07: 55: Open Discussion Conclusion Daniel K. Sodickson, M. D. , Ph. D.

After the meeting… • Results of this year’s call for abstracts and survey of Study Groups will be published on the ISMRM Web site • A web list of unsolved problems and unmet needs will be maintained and updated as a resources • Future possibilities: workshop, challenge grants, etc • Your suggestions? • Gather your submissions for next year…