Unsolved Problems and Unmet Needs in Magnetic Resonance

1
Unsolved Problems and Unmet Needs in Magnetic
Resonance

• Morning Categorical Course
• ISMRM 14th Scientific Meeting Exhibition
• Seattle, WA, USA
• May 9-12, 2005

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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.

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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.

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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. 

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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.

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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.

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Broader objectivesThe 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.

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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)

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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//www7.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)

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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?

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What do you mean by unsolved problems and unmet
needs?

• Survey of ISMRM Study Groups returned nearly 100
  items representing 7 Study Groups

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MR Engineering

1. Wireless or optical transmission of the MR signal
   out of the bore, to facilitate the use of large
   receiver coil arrays.
2. What number of channels is optimal/required for
   both receive (Parallel Imaging) and transmit
   (Transmit SENSE)
3. SAR how to control SAR at high fields (gt 3T),
   how to know where the hot spots are in vivo, how
   to monitor the SAR in the human body in real
   time.
4. Length of magnet/bore how short can it be? What
   are the limits in openness?
5. Actively shielded gt 7 T whole body magnets.
6. 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.
7. Reduction of acoustic noise to due switched
   magnetic field gradients, especially at high
   field.
8. Methods for imaging without the use of pulsed
   field gradients.
9. 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.
10. Practical methods for measuring the electrical
    properties of tissues using MRI.
11. 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).
12. A discussion board to draw an active group of
    engineers together for dissemination of knowledge
    and experience, rather than retainment in
    individual labs.

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High-Field

1. Solutions for the transmit B1 inhomogeneity at
   high field due to wavelength/dielectric effects.
2. Development of standardized method for SAR
   monitoring and setting SAR limits for multiple
   local transmit coils.
3. 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.
4. Acoustic noise reduction at high field.
5. Low noise, high fidelity, and powerful gradient
   amplifiers.
6. Development of an actively shielded 7 T
   whole-body sized magnet.
7. Fast CSI pulse sequences.
8. Pulse sequences for clinical applications of
   hetero-nucleus imaging (such as 3Li, 31P, 17O,
   etc.)
9. Detection of molecular probes that can pass
   through the blood-brain barrier and selectively
   bind to specific cells or tissues.
10. A method for identifying areal boundaries via
    high resolution MRI (to allow definition of
    functional areas on individual subjects).
11. Long-term health consequences of exposure to very
    high magnetic field.
12. Methods to remove magnetic susceptibility-induced
    image distortion.

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Diffusion/Perfusion

1. Definitively quantify the contributions of the
   intra- and extra-cellular components to the
   diffusion signal
2. Measure brain perfusion in acute stroke patients
   accurately enough to be useful Score 27
   Number of votes 7
3. Have realistic phantoms for diffusion imaging
   Score 26 Number of votes 11
4. Quantify connectivity between different regions,
   separated by different distances, reliably and
   consistently Score 25 Number of votes 8
5. Have an accepted and practical gold standard for
   tract tracing in the human brain Score 23
   Number of votes 7
6. Reliably measure the vascular territories of
   individual arteries Score 21 Number of votes
   6
7. Better understand the biophysical nature of
   diffusion MR signal, in order to optimize
   diffusion experiments more effectively Score
   20 Number of votes 4
8. Have a definitive, reproducible and easy way of
   calibrating ASL experiments with respect to M0
   (of tissue or blood, depending on the model) in
   order to get quantitative CBF values Score
   18 Number of votes 4
9. Use diffusion-derived measures, other than the
   mean diffusivity, in a clinical manner Score
   16 Number of votes 5
10. Have standard post-processing software
    (including motion correction) for ASL integrated
    onto a clinical scanner Score 16 Number of
    votes 5
11. Perform meaningful group comparisons on low
    dimensionality diffusion data (scalar invariants
    of the tensor), even if we dont understand the
    biophysical mechanisms underlying them /
    Perform meaningful voxel-based comparisons of
    DTI data Score 16 Number of votes 4
12. Reliably quantify the dependence of diffusion on
    diffusion time, to identify different tissue
    types or geometrical features Score 15
    Number of votes 5
13. Have realistic phantoms for perfusion imaging
    Score 15 Number of votes 5
14. Use DTI to reliably discriminate tumor
    infiltration from bland (tumorfree) edema Score
    14 Number of votes 5
15. Use arterial spin labeling to measure perfusion
    in white matter Score 14 Number of votes
    3
16. "Establish the definitive biophysical mechanism
    underlying the dependence of ADC on the b-value
    in the brain". Score 12 Number of votes 4
17. Resolve the topological ambiguity in diffusion
    displacement profiles (cross, kiss, twist, bend)
    Score 11 Number of votes 4
18. 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 lt 600 s/mm2
    or bgt 3000 s/mm2) Score 11 Number of votes
    4
19. Identify the cellular correlates of changes in
    diffusion anisotropy in white matter Score
    11 Number of votes 5

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MSK

1. Applications of Parallel Imaging in MSK MRI
2. New coils for 3T and 7T phased array, small
   coils
3. Kinematic and loaded imaging of joints and spine
4. Novel sequences to image cartilage including SSFP
   and uTE
5. Automated segmentation and parameter mapping
   software (morphology, T1, T2, T1rho)
6. Spectroscopy for MSK MRI - muscle, spine,
   cartilage (1H, 31P, Na)
7. Fat saturation for low field - robust Dixon
   imaging
8. New hardware gradient inserts and dedicated
   extremity 3T systems
9. Fast T1 and T1rho mapping sequences
10. DWI and DTI imaging for muscle and nerves
11. Marrow Imaging

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Flow and Motion

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

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Dynamic MR

• 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
  B0 field penetrating the body to organ depth.b.
  Overcome B0 field inhomogeneities.c. Create
  reasonably linear B0 gradientsd. Compensate for
  the residual non-linearity of the gradients.e.
  Have MRI sequences with only adiabatic pulsesf.
  Have enough B1 penetration for the adiabatic
  pulse without exceeding SAR limits.
• Create The mother of all sequences (so named by
  Paul Bottomley), a truly high resolution 3D pulse
  sequence that in a reasonably short scan time
  measures spin density, T1 and T2. Then use this
  information to generate any slice at any oblique
  angle with any T1 or T2 weighted contrast. This
  would replace the series of scout images, oblique
  scouts, T1 and T2 weighted images that usually
  make examinations long.
• Measure real time changes in spin density at a
  time scale shorter than T1. Example measure real
  time changes in phosphorous metabolites or in
  intracellular sodium in vivo in muscle or other
  excitable tissue.
• Measure changes in T1 at a time scale shorter
  than T1.
• 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.

White Matter
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This years 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

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This years 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?

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Tuesday

• What are we missing?  Seeing through metal and
  divining with RF coils
• Moderators Stuart Crozier, Michael Smith
• 0700 Introduction Daniel K. Sodickson,
  M.D., Ph.D.
• 0715 Techniques for MR Imaging Near
  Metallic Implants Garry E. Gold, M.D.
• 0730 Prospects of Absolute B1 Calibration
  Florian Wiesinger, Ph.D.
• 0745 Open Discussion

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Wednesday

• Can MRI provide a noninvasive biopsy?
• Moderators Michael Moseley, John Detre
• 0700 Cytoarchitectonic MRI  Can MRI Be
  Used to Quantify Neural Tissue? Itamar
  Ronen, Ph.D.
• 0715 Tissue Structure through Diffusion and
  Transverse Relaxation Measurements Valerij
  G. Kiselev, Ph.D.
• 0730 Unresolved Issues in Diffusion and
  Perfusion MRI  A Consensus from the Study
  Group Derek K. Jones, Ph.D.
• 0745 Open Discussion

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Thursday

• Will new contrast agents revolutionize MRI?
• Moderator Thomas Grist, Martin Prince
• 0700 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.
• 0715 Direct Detection of Neuromodulation
  Rachel Katz-Brull, Ph.D.
• 0730 Development of Status Tracers for
  Myocardial Perfusion Imaging by MRI Timothy
  F. Christian, M.D.
• 0745 Open Discussion

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Friday

• Do we need a virtual scanner, and do we
  understand real ones?
• Moderators David Hoult, Richard Bowtell
• 0700 Need for a Non-Commercial Open-Source MR
  Simulator Ralf B. Loeffler, Ph.D.
• 0715 Does the Principle of Reciprocity Hold at
  High Field MR? Jinghua Wang, Ph.D.
• 0730 Reciprocity at High Field Counterpoint
  David Hoult, Ph.D.
• 0740 Open Discussion
• 0755 Conclusion Daniel K. Sodickson, M.D.,
  Ph.D.

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After the meeting

• Results of this years 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