Government-Owned Inventions; Availability for Licensing: Methods for Improvements and Enhancements of Diffusion Tensor MRI, 17199-17201 [E9-8475]
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Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices
Licensing Contact: Jeffrey A. James,
PhD; 301–435–5474;
jeffreyja@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Mental Health,
Laboratory of Neuropsychology, is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
decoding algorithm for neuronal
responses. Please contact Suzanne
Winfield at winfiels@mail.nih.gov or
301–402–4324 for more information.
Dated: April 7, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–8473 Filed 4–13–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing: Methods for
Improvements and Enhancements of
Diffusion Tensor MRI
AGENCY:
National Institutes of Health,
HHS.
ACTION:
Notice.
The inventions listed below
are owned by an agency of the U.S.
Government and are available for
licensing in the U.S. in accordance with
35 U.S.C. 207 to achieve expeditious
commercialization of results of
Federally-funded research and
development. Foreign patent
applications are filed on selected
inventions to extend market coverage
for companies and may also be available
for licensing.
FOR FURTHER INFORMATION CONTACT:
Licensing information and copies of the
U.S. patent applications listed below
may be obtained by contacting either
Uri Reichman, PhD, MBA (Phone: 301–
435–4616; Fax: 301–402–0220; E-mail:
UR7a@nih.gov) or John Stansberry, PhD
(Phone: 301–435–5236; Fax: 301–402–
0220; E-mail: stansbej@mail.nih.gov) at
the Office of Technology Transfer,
National Institutes of Health, 6011
Executive Boulevard, Suite 325,
Rockville, Maryland 20852–3804. A
signed Confidential Disclosure
Agreement will be required to receive
copies of the patent applications.
SUPPLEMENTARY INFORMATION: The
technology offered for licensing is in the
field of Diffusion Magnetic Resonance
Imaging (MRI). Specifically, three new
SUMMARY:
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16:39 Apr 13, 2009
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methods have been described and
claimed that enhance the scope and
applicability of Diffusion Tensor MRI
(DTI or DT–MRI).
The invention of DTI represented a
breakthrough in MRI. It provides a
method and system for measuring the
effective diffusion tensor of spin-labeled
molecules, and for generating images of
key tensor-derived parameters that
indicate features of tissue
microstructure, organization and even
physiological state. DTI data has
improved the diagnosis of a large
number of diseases, disorders, and
conditions, and is also being used
therapeutically, for instance, to aid
neurosurgical planning.
One of the pioneers in Diffusion MRI,
Dr. Peter Basser, a Principal Investigator
in NIH’s Eunice Kennedy Shriver
National Institute of Child Health and
Human Development (NICHD), is the
primary inventor of DTI. Dr. Basser’s
first contribution in this field is
described in US Patent #5,539,310
(issued July 23, 1996), entitled ‘‘Method
and System for Measuring the Diffusion
Tensor and for Diffusion Tensor
Imaging.’’ His new inventions
(described below) extend the specificity
and clinical value of diffusion MRI data,
particularly in elucidating fine
microstructural details and features that
are not detectable using DTI.
Diffusion Tensor and q-Space MRI
Specimen Characterization
Description of Technology
Diffusion Tensor MRI (DTI or DT–
MRI) provides information primarily
about how water diffuses in the
extracellular compartment of tissues,
where water mobility is hindered (i.e.,
where water diffuses freely but
encounters barriers from which it is
reflected). However, DTI does not
provide a complete characterization of
diffusion in the intracellular
compartment of some cells, particularly
myelinated axons, where water mobility
is restricted by impermeable membranes
(i.e., where water is trapped but
otherwise free to diffuse within the
cell).
The subject invention provides a new
modeling framework that selfconsistently describes 3–D anisotropic
diffusion within a hindered
extracellular compartment and within a
restricted intra-axonal compartment. It
results in an improved characterization
and measurement tissue and cell
microstructure in neuronal tissue,
which promises to advance diagnosis of
neurological conditions (e.g., Stroke,
MS, Alzheimer’s disease), possibly
cognitive and behavioral disorders (e.g.,
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17199
schizophrenia), as well as our ability to
follow normal development and aging
processes.
More specifically, this new in vivo
diffusion MRI method, especially suited
for the characterization of brain white
matter, marries q-space and DTI
concepts: Diffusion within axons is
modeled as hindered diffusion parallel
to the axis of the axon, and restricted
diffusion perpendicular to the axis.
Diffusion exterior to axons is modeled
as hindered diffusion with differing
diffusivities parallel and perpendicular
to the nerves’ axis. To practice this
method, diffusion weighted (DW) MRI
data are acquired from specimens at
different q-values (with different
diffusion gradient magnitudes and
directions). Parameters associated with
tissue microstructure, such as the intra
and extra-axonal principal diffusivities
and their corresponding principal
directions, and the volume fractions of
intra and extra-axonal space are then
estimated from these data. Improved
angular resolution of fiber tract
orientation can be obtained for
tractography studies and more
microstructural information can be
gleaned for both diagnostic and
therapeutic purposes than from
conventional DTI. This technology has
been named CHARMED (Composite
Hindered and Restricted Model of
Diffusion).
Inventors
Peter J. Basser (NICHD) et al.
Publications
1. Y Assaf, RZ Freidlin, GK Rohde, PJ
Basser. New modeling and experimental
framework to characterize hindered and
restricted water diffusion in brain white
matter. Magn Reson Med. 2004
Nov;52(5):965–978.
2. Y Assaf and PJ Basser. Composite
hindered and restricted model of
diffusion (CHARMED) MR imaging of
the human brain. Neuroimage 2005 Aug
1;27(1):48–58.
¨
3. L Avram, E Ozarslan, Y Assaf, A
Bar-Shir, Y Cohen, PJ Basser. Threedimensional water diffusion in
impermeable cylindrical tubes: theory
versus experiments. NMR Biomed. 2008
Oct;21(8):888–898.
4. A Bar-Shir, L Avram, Y Assaf, PJ
Basser, Y Cohen. Experimental
Parameters and Diffraction Patterns at
High q Diffusion MR: Experiments and
Theoretical Simulations. Proc Intl Soc
Mag Reson Med. 2007;15:1530.
Patent Status
U.S. Patent Application No. 10/
888,917 filed 08 Jul 2004, claiming
E:\FR\FM\14APN1.SGM
14APN1
17200
Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices
priority to 08 Jul 2003 (HHS Reference
No. E–079–2003/0–US–02).
Non-Invasive in vivo MRI Axon
Diameter Measurement Methods
Description of Technology
This invention describes an
improvement and continuation of the
CHARMED MRI framework described
above, extending this technology to
measure the axon diameter distribution
(ADD) of nerve bundles (fascicles) in the
central and peripheral nervous systems.
The invention essentially consists of a
non-obvious combination of CHARMED
MRI and an improvement of an NMR
method, originally developed for
particle sizing in porous media
applications, which was extended and
enhanced to provide a direct
measurement of the ADD within nerve
fascicles in the brain, spine or other
parts of the peripheral nervous system
on a voxel-by-voxel basis. Additionally
this approach can be extended to
measure the fiber orientation
distribution of axons within each voxel
of an imaging volume and particularly
the myelin content within each voxel.
The significance of this invention is
that it represents a way to provide a
non-invasive, painless, in vivo
measurement of microanatomical
(histological) features of nerves (and
possibly muscles) that are critically
important in medicine and the
neurosciences and previously were only
available using invasive histological
means requiring biopsy. The ADD is
altered in abnormal development
(possibly even in autism), in
degenerative processes (e.g., aging,
alcoholism, Alzheimer’s disease) and
diseases such as ALS (Lou Gehrig’s
disease). The ADD is a critically
important parameter of a nerve bundle
from a neuroscience perspective
because axon diameter determines the
conduction velocity of action potentials,
and thus the arrival time and latency of
nerve impulses traveling along them.
The orientation or directional
distribution of axons is important in
Tractography applications to help
determine how different cortical regions
of the brain are connected to each other
via white matter pathways. Myelin is
dynamically regulated in vivo and
affects the electrical insulating property
of axons, and thus the conduction
velocity of nerves. Myelin content is a
critically important parameter in MS
and a large number of dysmyelinating
and demyelinating diseases as well as in
normal and abnormal development.
Inventors
Peter J. Basser (NICHD) et al.
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16:39 Apr 13, 2009
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Publications
1. Y Assaf, T Blumenfeld-Katzir, Y
Yovel, PJ Basser. AxCaliber: a method
for measuring axon diameter
distribution from diffusion MRI. Magn
Reson Med. 2008 Jun;59(6):1347–1354.
2. D Barazany, PJ Basser, Y Assaf. In
vivo measurement of axon diameter
distribution in the corpus callosum of
rat brain. Brain 2009; p 1–11.
3. D Barazany, PJ Basser, Y Assaf. Invivo measurement of the axon diameter
distribution in the rat’s corpus
callosum. In Proc Intl Soc Mag Reson
Med. 2008;16:567.
4. D Barazany, P Basser, Y Assaf.
AxCaliber—in-vivo measurement of
axon diameter distribution with MRI. In
16th Annual Meeting of The Israel
Society for Neuroscience, Eilat, Israel;
November 25–27, 2007; p. 8–9.
5. PJ Basser, T Blumenfeld, G Levin,
Y Yovel, Y Assaf. AxCaliber: an MRI
method to measure the diameter
distribution and density of axons in
neuronal tissue. In Magn Reson Imaging
2007;25:550.
6. Y Assaf and PJ Basser. Non
parametric approach for axon diameter
distribution estimation from diffusion
measurements. In Proc Intl Soc Mag
Reson Med. 2007;15:1536.
7. PJ Basser, T Blumenfeld, G Levin,
Y Yovel, Y Assaf. AxCaliber: an MRI
method to measure the diameter
distribution and density of axons in
neuronal tissue. In 8th International
Bologna Conference on Magnetic
Resonance in Porous Media 2006; p. 37.
8. Y Assaf, T Blumenfeld, G Levin, Y
Yovel, PJ Basser. AxCaliber—a method
to measure the axon diameter
distribution and density in neuronal
tissues. In Proc Intl Soc Mag Reson Med.
2006;14:637.
Patent Status
U.S. Patent Application No. 12/
114,713 filed 02 May 2008 (HHS
Reference No. E–079–2003/1–US–01),
which is a CIP of the above U.S. Patent
Application No. 10/888,917.
Magnetic Resonance Specimen
Evaluation Using Multiple Pulse Field
Gradient Sequences
Description of Technology
A further enhancement to the
diffusion MRI technologies described
above is offered in this further
extension. The invention proposes and
claims an MRI-method that is based on
the measurement and acquisition of
multiple pulsed field gradient (m-PFG)
rather than the previously used singlepulsed field gradient (s-PFG) MRI
sequences. In particular, double PFG (dPFG) sequences offer higher sensitivity
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and greater robustness, as it is more
sensitive to the effect of ‘‘restriction’’,
i.e., to water trapped within the axon’s
intracellular space, and thus to the
diameter of the axons. It renders the MR
sequence more sensitive to ‘‘pore size’’
and ‘‘pore shape’’ and thus makes the
measurement of the ADD more sensitive
and accurate. Moreover, measurements
using the multiple-PFG sequence can be
performed readily at ‘‘low b’’ or ‘‘low
q’’, making it biologically relevant and
clinically feasible.
Inventors
¨
Peter J. Basser and Evren Ozarslan
(NICHD).
Publications
¨
1. E Ozarslan and PJ Basser.
Microscopic anisotropy revealed by
NMR double pulsed field gradient
experiments with arbitrary timing
parameters. J Chem Phys 2008 Apr
21;128(15):154511.
2. ME Komlosh, MJ Lizak, F Horkay,
RZ Freidlin, PJ Basser. Observation of
microscopic diffusion anisotropy in the
spinal cord using double-pulsed
gradient spin echo MRI. Magn Reson in
Med. 2008 Apr;59(4):803–809.
¨
3. E Ozarslan and PJ Basser. MR
diffusion -‘‘diffraction’’ phenomenon in
multi-pulse-field-gradient experiments.
J Magn Reson. 2007 Oct;188(2):285–294.
4. ME Komlosh, F Horkay, RZ
Freidlin, U Nevo, Y Assaf, PJ Basser.
Detection of microscopic anisotropy in
gray matter and in a novel tissue
phantom using double Pulsed Gradient
Spin Echo MR. J Magn Reson. 2007
Nov;189(1):38–45.
5. ME Komlosh, RZ Freidlin, F
Horkay, Y Assaf, PJ Basser. Detection of
microscopic anisotropy in gray matter
using d-PGSE. In Proc Intl Soc Mag
Reson Med. 2005;13:843.
6. ME Komlosh, MJ Lizak, F Horkay,
RZ Friedlin, PJ Basser. (2006) Detection
of local anisotropy using double-PGSE
filtered imaging. In 47th Experimental
Nuclear Magnetic Resonance
Conference, 2006.
¨
7. E Ozarslan and PJ Basser. DiffusionDiffraction Phenomenon in multi-PFG
experiments. In Science Networking
Development Scheme Meeting. Ein–
Boqeq, Israel, 2007.
8. M E Komlosh, MJ Lizak, F Horkay,
RZ Freidlin, PJ Basser. Observation of
microscopic diffusion anisotropy in the
spinal cord using double-pulsed
gradient spin echo MRI. In Proc Intl Soc
Mag Reson Med. 2008;16:763.
¨
9. E Ozarslan and PJ Basser.
Microscopic anisotropy revealed by
double-PFG NMR. In 9th International
Bologna Conference on Magnetic
Resonance in Porous Media 2008; p. 26.
E:\FR\FM\14APN1.SGM
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Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices
¨
10. E Ozarslan, CG Koay, PJ Basser.
Double-PFG diffusion-diffraction in
ellipsoidal pores. In 9th International
Bologna Conference on Magnetic
Resonance in Porous Media 2008;
p. 115.
Licensing Contacts
Uri Reichman, PhD, MBA; 301–435–
4616; UR7a@nih.gov; John Stansberry,
PhD; 301–435–5236;
stansbej@mail.nih.gov.
Patent Status
U.S. Provisional Application No. 61/
087,968 filed 11 Aug 2008 (HHS
Reference No. E–276–2008/0–US–01).
Advantages
The three inventions described above
and collectively offered for licensing
offer a non-invasive, painless means for
measurement quantities such as the
axon diameter distribution (ADD) and
significant improvements in sensitivity
and robustness to existing MRI methods,
in particular for imaging of the Central
Nervous System, and for in vivo
measurement of microanatomical
(histological) features of nerves (and
possibly muscles) that are critically
important in medicine and in particular
in neuroscience. Furthermore, ADD is
altered in abnormal development
(possibly even in autism), in
degenerative process (e.g., aging,
alcoholism, Alzheimer’s disease) and
diseases such as ALS (Lou Gehrig’s
disease) and thus the improved
sensitivities offered by the subject
inventions is of utmost significance for
public health.
Development Status
These inventions are fully developed.
Market
The market for MRI in human
diagnostics is huge and rapidly growing.
The race to improve the sensitivities of
MRI measurement and to enhance the
capabilities of measuring and examining
fine structures in general, and in
neuroscience in particular is of
significant magnitude. The three
inventions described above may
collectively offer significant commercial
opportunity to MRI companies.
The market for medical imaging
equipment industry is approximately
$9.0 billion dollars now and has been
growing by approximately 7.6%
annually. MRI instrumentation
constitutes a significant portion of this
market.
Related Technology
U.S. Patent No. 5,539,310 issued 23
Jul 1996—‘‘Method and System for
Measuring the Diffusion Tensor and for
Diffusion Tensor Imaging’’ (HHS
Reference No. E–203–1993/0).
Licensing Status
Available for licensing.
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16:39 Apr 13, 2009
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Collaborative Research Opportunity
The Eunice Kennedy Shriver National
Institute of Child Health and Human
Development, Section on Tissue
Biophysics and Biomimetics, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize novel MRI methods to
probe tissue structure and organization,
particularly for neuroimaging
applications. Please contact Alan
Hubbs, PhD at 301–594–4263 or
hubbsa@mail.nih.gov for more
information.
Dated: April 7, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–8475 Filed 4–13–09; 8:45 am]
BILLING CODE 4140–01–P
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HUMAN SERVICES
National Institutes of Health
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the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
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applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute of
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Date: April 20, 2009.
Time: 2 p.m. to 4 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6101
Executive Boulevard, Rockville, MD 20852,
(Telephone Conference Call)
Contact Person: Shanta Rajaram, PhD,
Scientific Review Administrator, Scientific
Review Branch, Division Of Extramural
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17201
Research, NINDS/NIH/DHHS/Neuroscience
Center, 6001 Executive Blvd., Suite 3208,
MSC9529, Bethesda, MD 20852, (301) 435–
6033, rajarams@mail.nih.gov.
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Related to Neurological Disorders; 93.854,
Biological Basis Research in the
Neurosciences, National Institutes of Health,
HHS)
Dated: April 7, 2009.
Anna Snouffer,
Deputy Director, Office of Federal Advisory
Committee Policy.
[FR Doc. E9–8471 Filed 4–13–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Eunice Kennedy Shriver National
Institute of Child Health & Human
Development; Notice of Meeting
Pursuant to section 10(a) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
The meeting will be open to the
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Date: May 6, 2009.
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E:\FR\FM\14APN1.SGM
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]]>Agencies
[Federal Register Volume 74, Number 70 (Tuesday, April 14, 2009)]
[Notices]
[Pages 17199-17201]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-8475]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing: Methods
for Improvements and Enhancements of Diffusion Tensor MRI
AGENCY: National Institutes of Health, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The inventions listed below are owned by an agency of the U.S.
Government and are available for licensing in the U.S. in accordance
with 35 U.S.C. 207 to achieve expeditious commercialization of results
of Federally-funded research and development. Foreign patent
applications are filed on selected inventions to extend market coverage
for companies and may also be available for licensing.
FOR FURTHER INFORMATION CONTACT: Licensing information and copies of
the U.S. patent applications listed below may be obtained by contacting
either Uri Reichman, PhD, MBA (Phone: 301-435-4616; Fax: 301-402-0220;
E-mail: UR7a@nih.gov) or John Stansberry, PhD (Phone: 301-435-5236;
Fax: 301-402-0220; E-mail: stansbej@mail.nih.gov) at the Office of
Technology Transfer, National Institutes of Health, 6011 Executive
Boulevard, Suite 325, Rockville, Maryland 20852-3804. A signed
Confidential Disclosure Agreement will be required to receive copies of
the patent applications.
SUPPLEMENTARY INFORMATION: The technology offered for licensing is in
the field of Diffusion Magnetic Resonance Imaging (MRI). Specifically,
three new methods have been described and claimed that enhance the
scope and applicability of Diffusion Tensor MRI (DTI or DT-MRI).
The invention of DTI represented a breakthrough in MRI. It provides
a method and system for measuring the effective diffusion tensor of
spin-labeled molecules, and for generating images of key tensor-derived
parameters that indicate features of tissue microstructure,
organization and even physiological state. DTI data has improved the
diagnosis of a large number of diseases, disorders, and conditions, and
is also being used therapeutically, for instance, to aid neurosurgical
planning.
One of the pioneers in Diffusion MRI, Dr. Peter Basser, a Principal
Investigator in NIH's Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), is the primary inventor of
DTI. Dr. Basser's first contribution in this field is described in US
Patent 5,539,310 (issued July 23, 1996), entitled ``Method and
System for Measuring the Diffusion Tensor and for Diffusion Tensor
Imaging.'' His new inventions (described below) extend the specificity
and clinical value of diffusion MRI data, particularly in elucidating
fine microstructural details and features that are not detectable using
DTI.
Diffusion Tensor and q-Space MRI Specimen Characterization
Description of Technology
Diffusion Tensor MRI (DTI or DT-MRI) provides information primarily
about how water diffuses in the extracellular compartment of tissues,
where water mobility is hindered (i.e., where water diffuses freely but
encounters barriers from which it is reflected). However, DTI does not
provide a complete characterization of diffusion in the intracellular
compartment of some cells, particularly myelinated axons, where water
mobility is restricted by impermeable membranes (i.e., where water is
trapped but otherwise free to diffuse within the cell).
The subject invention provides a new modeling framework that self-
consistently describes 3-D anisotropic diffusion within a hindered
extracellular compartment and within a restricted intra-axonal
compartment. It results in an improved characterization and measurement
tissue and cell microstructure in neuronal tissue, which promises to
advance diagnosis of neurological conditions (e.g., Stroke, MS,
Alzheimer's disease), possibly cognitive and behavioral disorders
(e.g., schizophrenia), as well as our ability to follow normal
development and aging processes.
More specifically, this new in vivo diffusion MRI method,
especially suited for the characterization of brain white matter,
marries q-space and DTI concepts: Diffusion within axons is modeled as
hindered diffusion parallel to the axis of the axon, and restricted
diffusion perpendicular to the axis. Diffusion exterior to axons is
modeled as hindered diffusion with differing diffusivities parallel and
perpendicular to the nerves' axis. To practice this method, diffusion
weighted (DW) MRI data are acquired from specimens at different q-
values (with different diffusion gradient magnitudes and directions).
Parameters associated with tissue microstructure, such as the intra and
extra-axonal principal diffusivities and their corresponding principal
directions, and the volume fractions of intra and extra-axonal space
are then estimated from these data. Improved angular resolution of
fiber tract orientation can be obtained for tractography studies and
more microstructural information can be gleaned for both diagnostic and
therapeutic purposes than from conventional DTI. This technology has
been named CHARMED (Composite Hindered and Restricted Model of
Diffusion).
Inventors
Peter J. Basser (NICHD) et al.
Publications
1. Y Assaf, RZ Freidlin, GK Rohde, PJ Basser. New modeling and
experimental framework to characterize hindered and restricted water
diffusion in brain white matter. Magn Reson Med. 2004 Nov;52(5):965-
978.
2. Y Assaf and PJ Basser. Composite hindered and restricted model
of diffusion (CHARMED) MR imaging of the human brain. Neuroimage 2005
Aug 1;27(1):48-58.
3. L Avram, E [Ouml]zarslan, Y Assaf, A Bar-Shir, Y Cohen, PJ
Basser. Three-dimensional water diffusion in impermeable cylindrical
tubes: theory versus experiments. NMR Biomed. 2008 Oct;21(8):888-898.
4. A Bar-Shir, L Avram, Y Assaf, PJ Basser, Y Cohen. Experimental
Parameters and Diffraction Patterns at High q Diffusion MR: Experiments
and Theoretical Simulations. Proc Intl Soc Mag Reson Med. 2007;15:1530.
Patent Status
U.S. Patent Application No. 10/888,917 filed 08 Jul 2004, claiming
[[Page 17200]]
priority to 08 Jul 2003 (HHS Reference No. E-079-2003/0-US-02).
Non-Invasive in vivo MRI Axon Diameter Measurement Methods
Description of Technology
This invention describes an improvement and continuation of the
CHARMED MRI framework described above, extending this technology to
measure the axon diameter distribution (ADD) of nerve bundles
(fascicles) in the central and peripheral nervous systems.
The invention essentially consists of a non-obvious combination of
CHARMED MRI and an improvement of an NMR method, originally developed
for particle sizing in porous media applications, which was extended
and enhanced to provide a direct measurement of the ADD within nerve
fascicles in the brain, spine or other parts of the peripheral nervous
system on a voxel-by-voxel basis. Additionally this approach can be
extended to measure the fiber orientation distribution of axons within
each voxel of an imaging volume and particularly the myelin content
within each voxel.
The significance of this invention is that it represents a way to
provide a non-invasive, painless, in vivo measurement of
microanatomical (histological) features of nerves (and possibly
muscles) that are critically important in medicine and the
neurosciences and previously were only available using invasive
histological means requiring biopsy. The ADD is altered in abnormal
development (possibly even in autism), in degenerative processes (e.g.,
aging, alcoholism, Alzheimer's disease) and diseases such as ALS (Lou
Gehrig's disease). The ADD is a critically important parameter of a
nerve bundle from a neuroscience perspective because axon diameter
determines the conduction velocity of action potentials, and thus the
arrival time and latency of nerve impulses traveling along them. The
orientation or directional distribution of axons is important in
Tractography applications to help determine how different cortical
regions of the brain are connected to each other via white matter
pathways. Myelin is dynamically regulated in vivo and affects the
electrical insulating property of axons, and thus the conduction
velocity of nerves. Myelin content is a critically important parameter
in MS and a large number of dysmyelinating and demyelinating diseases
as well as in normal and abnormal development.
Inventors
Peter J. Basser (NICHD) et al.
Publications
1. Y Assaf, T Blumenfeld-Katzir, Y Yovel, PJ Basser. AxCaliber: a
method for measuring axon diameter distribution from diffusion MRI.
Magn Reson Med. 2008 Jun;59(6):1347-1354.
2. D Barazany, PJ Basser, Y Assaf. In vivo measurement of axon
diameter distribution in the corpus callosum of rat brain. Brain 2009;
p 1-11.
3. D Barazany, PJ Basser, Y Assaf. In-vivo measurement of the axon
diameter distribution in the rat's corpus callosum. In Proc Intl Soc
Mag Reson Med. 2008;16:567.
4. D Barazany, P Basser, Y Assaf. AxCaliber--in-vivo measurement of
axon diameter distribution with MRI. In 16th Annual Meeting of The
Israel Society for Neuroscience, Eilat, Israel; November 25-27, 2007;
p. 8-9.
5. PJ Basser, T Blumenfeld, G Levin, Y Yovel, Y Assaf. AxCaliber:
an MRI method to measure the diameter distribution and density of axons
in neuronal tissue. In Magn Reson Imaging 2007;25:550.
6. Y Assaf and PJ Basser. Non parametric approach for axon diameter
distribution estimation from diffusion measurements. In Proc Intl Soc
Mag Reson Med. 2007;15:1536.
7. PJ Basser, T Blumenfeld, G Levin, Y Yovel, Y Assaf. AxCaliber:
an MRI method to measure the diameter distribution and density of axons
in neuronal tissue. In 8th International Bologna Conference on Magnetic
Resonance in Porous Media 2006; p. 37.
8. Y Assaf, T Blumenfeld, G Levin, Y Yovel, PJ Basser. AxCaliber--a
method to measure the axon diameter distribution and density in
neuronal tissues. In Proc Intl Soc Mag Reson Med. 2006;14:637.
Patent Status
U.S. Patent Application No. 12/114,713 filed 02 May 2008 (HHS
Reference No. E-079-2003/1-US-01), which is a CIP of the above U.S.
Patent Application No. 10/888,917.
Magnetic Resonance Specimen Evaluation Using Multiple Pulse Field
Gradient Sequences
Description of Technology
A further enhancement to the diffusion MRI technologies described
above is offered in this further extension. The invention proposes and
claims an MRI-method that is based on the measurement and acquisition
of multiple pulsed field gradient (m-PFG) rather than the previously
used single-pulsed field gradient (s-PFG) MRI sequences. In particular,
double PFG (d-PFG) sequences offer higher sensitivity and greater
robustness, as it is more sensitive to the effect of ``restriction'',
i.e., to water trapped within the axon's intracellular space, and thus
to the diameter of the axons. It renders the MR sequence more sensitive
to ``pore size'' and ``pore shape'' and thus makes the measurement of
the ADD more sensitive and accurate. Moreover, measurements using the
multiple-PFG sequence can be performed readily at ``low b'' or ``low
q'', making it biologically relevant and clinically feasible.
Inventors
Peter J. Basser and Evren [Ouml]zarslan (NICHD).
Publications
1. E [Ouml]zarslan and PJ Basser. Microscopic anisotropy revealed
by NMR double pulsed field gradient experiments with arbitrary timing
parameters. J Chem Phys 2008 Apr 21;128(15):154511.
2. ME Komlosh, MJ Lizak, F Horkay, RZ Freidlin, PJ Basser.
Observation of microscopic diffusion anisotropy in the spinal cord
using double-pulsed gradient spin echo MRI. Magn Reson in Med. 2008
Apr;59(4):803-809.
3. E [Ouml]zarslan and PJ Basser. MR diffusion -``diffraction''
phenomenon in multi-pulse-field-gradient experiments. J Magn Reson.
2007 Oct;188(2):285-294.
4. ME Komlosh, F Horkay, RZ Freidlin, U Nevo, Y Assaf, PJ Basser.
Detection of microscopic anisotropy in gray matter and in a novel
tissue phantom using double Pulsed Gradient Spin Echo MR. J Magn Reson.
2007 Nov;189(1):38-45.
5. ME Komlosh, RZ Freidlin, F Horkay, Y Assaf, PJ Basser. Detection
of microscopic anisotropy in gray matter using d-PGSE. In Proc Intl Soc
Mag Reson Med. 2005;13:843.
6. ME Komlosh, MJ Lizak, F Horkay, RZ Friedlin, PJ Basser. (2006)
Detection of local anisotropy using double-PGSE filtered imaging. In
47th Experimental Nuclear Magnetic Resonance Conference, 2006.
7. E [Ouml]zarslan and PJ Basser. Diffusion-Diffraction Phenomenon
in multi-PFG experiments. In Science Networking Development Scheme
Meeting. Ein-Boqeq, Israel, 2007.
8. M E Komlosh, MJ Lizak, F Horkay, RZ Freidlin, PJ Basser.
Observation of microscopic diffusion anisotropy in the spinal cord
using double-pulsed gradient spin echo MRI. In Proc Intl Soc Mag Reson
Med. 2008;16:763.
9. E [Ouml]zarslan and PJ Basser. Microscopic anisotropy revealed
by double-PFG NMR. In 9th International Bologna Conference on Magnetic
Resonance in Porous Media 2008; p. 26.
[[Page 17201]]
10. E [Ouml]zarslan, CG Koay, PJ Basser. Double-PFG diffusion-
diffraction in ellipsoidal pores. In 9th International Bologna
Conference on Magnetic Resonance in Porous Media 2008; p. 115.
Patent Status
U.S. Provisional Application No. 61/087,968 filed 11 Aug 2008 (HHS
Reference No. E-276-2008/0-US-01).
Advantages
The three inventions described above and collectively offered for
licensing offer a non-invasive, painless means for measurement
quantities such as the axon diameter distribution (ADD) and significant
improvements in sensitivity and robustness to existing MRI methods, in
particular for imaging of the Central Nervous System, and for in vivo
measurement of microanatomical (histological) features of nerves (and
possibly muscles) that are critically important in medicine and in
particular in neuroscience. Furthermore, ADD is altered in abnormal
development (possibly even in autism), in degenerative process (e.g.,
aging, alcoholism, Alzheimer's disease) and diseases such as ALS (Lou
Gehrig's disease) and thus the improved sensitivities offered by the
subject inventions is of utmost significance for public health.
Development Status
These inventions are fully developed.
Market
The market for MRI in human diagnostics is huge and rapidly
growing. The race to improve the sensitivities of MRI measurement and
to enhance the capabilities of measuring and examining fine structures
in general, and in neuroscience in particular is of significant
magnitude. The three inventions described above may collectively offer
significant commercial opportunity to MRI companies.
The market for medical imaging equipment industry is approximately
$9.0 billion dollars now and has been growing by approximately 7.6%
annually. MRI instrumentation constitutes a significant portion of this
market.
Related Technology
U.S. Patent No. 5,539,310 issued 23 Jul 1996--``Method and System
for Measuring the Diffusion Tensor and for Diffusion Tensor Imaging''
(HHS Reference No. E-203-1993/0).
Licensing Status
Available for licensing.
Licensing Contacts
Uri Reichman, PhD, MBA; 301-435-4616; UR7a@nih.gov; John
Stansberry, PhD; 301-435-5236; stansbej@mail.nih.gov.
Collaborative Research Opportunity
The Eunice Kennedy Shriver National Institute of Child Health and
Human Development, Section on Tissue Biophysics and Biomimetics, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
novel MRI methods to probe tissue structure and organization,
particularly for neuroimaging applications. Please contact Alan Hubbs,
PhD at 301-594-4263 or hubbsa@mail.nih.gov for more information.
Dated: April 7, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-8475 Filed 4-13-09; 8:45 am]
BILLING CODE 4140-01-P
