Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices 17199 

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. 

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 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., 

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 O ̈ zarslan, 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 

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. 

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 

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 O ̈ zarslan 

(NICHD). 

Publications 

1. E O ̈ 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 O ̈ 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 O ̈ zarslan 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 O ̈ 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. 

Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices 17201 

10. E O ̈ 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Neurological 

Disorders and Stroke; Notice of Closed 

Meeting 

Pursuant to section 10(d) 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 closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute of 

Neurological Disorders and Stroke Special 

Emphasis Panel; Clinical Trials in Motor 

Neuron Disease. 

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 

Research, NINDS/NIH/DHHS/Neuroscience 

Center, 6001 Executive Blvd., Suite 3208, 

MSC9529, Bethesda, MD 20852, (301) 435– 

6033, rajarams@mail.nih.gov. 

This notice is being published less than 15 

days prior to the meeting due to the timing 

limitations imposed by the review and 

funding cycle. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.853, Clinical Research 

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 

public, with attendance limited to space 

available. Individuals who plan to 

attend and need special assistance, such 

as sign language interpretation or other 

reasonable accommodations, should 

notify the Contact Person listed below 

in advance of the meeting. 

Name of Committee: National Institute of 

Child Health and Human Development 

Special Emphasis Panel; ‘‘Comparative 

Evaluation of Assisted Reproductive 

Technologies and Birth Outcomes’’. 

Date: May 6, 2009. 

Time: 2 p.m. to 3 p.m. 

Agenda: To provide concept review of 

proposed concept review. 

Place: National Institutes of Health, 6100 

Executive Boulevard, Room 5B01, Rockville, 

MD 20852 (Telephone Conference Call). 

Contact Person: Sathasiva B. Kandasamy, 

PhD, Scientific Review Administrator, 

Division of Scientific Review, National 

Institute of Child Health and Human 

Development, 6100 Executive Boulevard, 

Room 5b01, Bethesda, MD 20892–9304, (301) 

435–6680, skandasa@mail.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.864, Population Research; 

93.865, Research for Mothers and Children; 

93.929, Center for Medical Rehabilitation 

Research; 93.209, Contraception and 

Infertility Loan Repayment Program, National 

Institutes of Health, HHS)