Notice (B): Government-Owned Inventions; Availability for Licensing

Federal Register: December 31, 2009 (Volume 74, Number 250)            
                  Page 69346-69348

AGENCY: National Institutes of Health, Public Health Service, 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.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Fourier X-ray Scattering and Phase-Contrast Imaging: Enhanced Contrast 
and Sensitivity of X-ray Images

    Description of Technology: The invention offered for licensing is 
broadly applicable to medical diagnostic imaging, biological imaging, 
industrial non-destructive testing, security screening, and other 
routine x-ray inspections. The invention provides a method and 
apparatus that can significantly improve and enhance the contrast and 
sensitivity of x-ray images. More specifically, the method described in 
the invention provides a technique to obtain in a single shot x-ray 
diffraction, differential phase-contrast, as well as the conventional 
absorption images. X-ray diffraction reveals information about 
microscopic structures in the imaged object from nanometer to 
micrometer scales which enables detection of specific materials and 
disease pathologies that are invisible in conventional x-ray images. 
The main advantage of the invention over prior art is the single-shot 
capability without the need to scan an analyzer crystal or grating, and 
without the need for any hardware beyond standard radiography 
equipment. It also offers flexibility in hardware configuration to 
target specific materials by their diffraction signature. For this 
reason the invention is highly adaptable and well suited for day-to-day 
applications of x-ray radiography and computed tomography.
    In one of the embodiments of the invention for example, a 
scattering imaging method uses a transmission grid to modulate the 
intensity of a beam of an x-ray radiation source. A detector captures a 
raw image from the modulated intensity pattern. A diffraction image can 
be automatically generated from the detected modulated intensity 
pattern.
    In yet another embodiment, both a diffraction image and a 
differential phase-contrast image are obtained in a single exposure. 
Advantageously, commercially available x-ray grids and radiography 
machines can be used for this method, and exact positioning of the grid 
is unnecessary, as the method works for any non-zero distance between 
the grid and the detector. Thus, the speed and ease of implementation 
makes it suitable for both planar radiography and 3D computed 
tomography. In addition to its medical diagnostics significance, the 
invention can be utilized in other, non-medical applications such as 
non-destructive inspections and security screening.

Applications

     Medical diagnostic radiography and computed tomography. 
For example, imaging blood vessels, imaging of bones (i.e., 
osteoporosis, fractures).
     Non-invasive characterization of material microscopic 
structures by planar radiography or 3D computed tomography 
implementations of the invention.
     Detection of materials by their diffraction signature in 
x-ray inspections and security screening.
    Advantages: Although x-ray diffraction and phase-contrast imaging 
can detect materials and structures that are invisible by conventional 
absorption images, current techniques remain difficult to implement due 
to requirements for specialized x-ray optical components and/or 
brilliant sources, and lengthy scanning of analyzer components such as 
perfect crystals or high-density gratings. A recent publication 
(US2007/0183563 A1) mentioned that by using a detector with elements 
less than \1/3\ of the pitch of an analyzer grating, it is possible to 
obtain differential phase-contrast images in one measurement without 
the need to scan. US2007/0183580 A1 further elaborates on this 
technique and specifies that the detector elements are an integer 
fraction of the grating pitch so that sub-groups of the detectors can 
report x-ray intensities of different portions of a grating period, 
from which the phase shift of the grating pattern is measured. Such 
detectors are highly challenging to realize, and are not able to cope 
with varying pitches or patterns of x-ray beam modulation.
    It is additionally known in the art to remove the effects of 
scattering with the use of grids, gratings, or other masks of 
periodically arranged opaque areas. Specifically, a mask or multiple 
masks of periodically arranged opaque areas are placed in the x-ray 
path, such that periodic dark shadows are created on a recorder surface 
either by direct geometric shadowing or by wave-interference effects. 
The shadow areas only receive x-ray which is scattered in the object. 
The signals of these shadow areas are subtracted from the raw image to 
yield an image free of the effects of scattering.
    Nonetheless, the above variations require exacting procedures or 
are expensive, making the prior art ill-suited for today's routine x-
ray imaging applications, including non-destructive testing (e.g., 
component inspection without damage), security screening, and medical 
diagnostic exams.
    The present technology overcomes the drawbacks of the prior art by 
allowing the acquisition of x-ray diffraction, differential phase-
contrast and absorption images all in a single exposure without the 
need for scanning or any hardware beyond commercial radiography 
equipment.
    It is particularly flexible when compared to prior art in that the 
number of transmission grids, their patterns and their positions can 
all be adjusted to selectively detect or enhance specific materials, 
such as contrast agents in medical diagnostic imaging or explosive 
materials in security screening.
    Development Status: The invention is fully developed.

[[Page 69347]]

    Market: The market for medical imaging equipment industry is 
approximately $9.0 billion dollars now and has been growing by 
approximately 7.6% annually. X-ray imaging and related instrumentation 
constitutes a significant portion of this market.
     X-ray radiography is the most common and widely available 
diagnostic imaging technique. Even when a diagnostic testing requires 
more powerful or sophisticated tests, an x-ray imaging may many times 
be needed first before other more sophisticated tests are applied.
     X-ray angiography currently provides the best 
visualization of blood vessels in the body. The ability of this 
technology to selectively enhance contrast agents can eliminate 
difficulties associated with subtraction angiography and improve 
angiography exams.
     The advent of Computed Tomography (CT) and other digital 
x-ray technologies have enhanced the capabilities of x-ray imaging and 
have resulted in the tremendous growth of x-ray imaging. CT combines x-
rays with computer technology and can produce a highly detailed, cross-
sectional image of the body and organs, tissues or tumors inside the 
body. CT scans are now routinely used to diagnose problems with small, 
bony structures or in cases of severe trauma to the brain, spinal cord, 
chest, abdomen, or pelvis. Furthermore, the introduction of multi-slice 
CT has been one of the most significant enhancements ever brought to 
the market, and the technological innovations that have been made 
within the realm of CT in recent years are revolutionary and should be 
the primary drivers for future industry growth. Electron Beam 
Technology (EBT) for example is a CT technology that created 
opportunities in cardiac diagnostics. CT requires fast and robust image 
acquisition, thus the present invention is uniquely able to enhance CT 
with diffraction and phase contrast.
     The United States market for computed tomography (CT) 
scanning systems is estimated to touch $3.6 billion by the end of 2009. 
The U.S. accounts for over 50.0 percent of the worldwide market. 
Cardiac imaging is a fast expanding CT application due to its utility 
in emergency medicine, perfusion studies and CT angiography. While 
hospitals started out as the original care site where scanning was 
done, independent imaging centers and physician's offices offering 
scanning have become widespread in the U.S. over the last decade. With 
the advent of portable and mobile CT scans, access and availability of 
this imaging modality has increased significantly. Currently it is 
estimated that about 25% of scanning stations are in private practices 
and imaging centers that are not part of a hospital. Most hospitals 
have a range of scanners from low-slice to high-slice. The overall 
trend is towards acquiring high-slice scanners which can be similar in 
terms of capital costs but far superior in function.
     One of the fastest growing applications is CT angiograms, 
currently at an annual rate of about half a million in the U.S. 
Pediatric usage is also growing. An estimated 6 million CT scans per 
year are done for pediatric cases. Of these, about 600,000 are done for 
head and abdominal examinations. The ability of the present technology 
to highlight certain contrast agents against background tissue and bone 
signal can significantly enhance CT angiography.
     The women's mammography segment of x-ray imaging is poised 
for a major new phase of growth fueled by the availability of new 
technology coming out of the computer and digital areas and the higher 
interest of individual patients and general healthcare consumers to 
take charge of their own health status. Continuous improvements in 
technology are resulting in a growing number of new imaging diagnostic 
tests that combine high levels of accuracy with rapid, easy-to-use 
product formats. Digital mammography is driving more screening 
programs.
     X-ray inspection in product quality control and in 
security screening. The present technology offers the ability to detect 
and target materials based on their x-ray diffraction signatures. It 
may significantly enhance the sensitivity and specificity of the 
inspection.
    The present technology provides enhancement in x-ray imaging, thus 
its application in x-ray instrumentation, offers excellent commercial 
opportunities given the size of the industry.
    Inventors: Han Wen (NHLBI).

Related Publications

    1. Wen H, Bennett EE, Hegedus MM, Rapacchi S. Fourier X-ray 
scattering radiography yields bone structural information. Radiology 
2009 Jun;252(3):910-918.
    2. Wen H, Bennett E, Hegedus MM, Carroll SC. Spatial harmonic 
imaging of X-ray scattering--initial results. IEEE Trans Med Imaging 
2008 Aug;27(8):997-1002.
    Patent Status: PCT Application No. PCT/US2009/051642 filed 24 Jul 
2009 (HHS Reference No. E-248-2009/0-PCT-01).
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, PhD, MBA; 301-435-4616; 
UR7a@nih.gov; or John Stansberry, PhD; 301-435-5236; 
stansbej@mail.nih.gov.
    Collaborative Research Opportunity: The National Heart, Lung, and 
Blood Institute, Laboratory of Cardiac Energetics, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
single-shot x-ray diffraction and phase-contrast imaging. Please 
contact Denise Crooks at 301-402-5579 or crooksd@nhlbi.nih.gov for more 
information.

Non-Contact Total Emission Detection Methods for Multiphoton 
Microscopy: Improved Image Fidelity and Biological Sample Analysis

    Description of Technology: The technology offered for licensing and 
for further development is in the field of multiphoton microscopy 
(MPM). More specifically, the invention describes and claims optical 
designs that can enhance and extend the capabilities of MPM in spectral 
imaging of biological samples. The unique design of the light 
collection and the detection optics maximizes the collection of emitted 
light, thus increasing the signal and hence the signal-to-noise ratio 
(SNR). Improvement in image fidelity will result in improved analysis 
of biological samples and thus will favorably impact medical research 
and possibly clinical diagnosis. The present technology is a further 
improvement on the TED (Total Emission Detection) technology, first 
disclosed by Dr. Robert Balaban et al. at the NIH in 2006 and claimed 
in U.S. patent application 11/979,600, now allowed (Patent Publication 
US-2008-0063345 A1, March 13, 2008). The earlier NIH TED technology 
proposed an optical design based on enveloping the entirety of a small 
sample in a parabolic mirror/condenser combination so light emanated by 
a sample in all directions is redirected to the detector. The present 
technology further expands the capabilities of TED as its unique design 
employing parabolic, toric and conic mirrors ensures maximum light 
collection from large samples in cases where there is only access to 
one side of the tissues (e.g., in vivo or ex vivo). This is 
accomplished by the redirection of all attainable light (i.e., light 
escaping the tissue or a whole animal in the epi and sideway 
directions) to the detector.

Applications

     Tissue and cell analysis in biomedical research.
     Potential applications in clinical diagnostics.

[[Page 69348]]

    Advantages: The advent of multiphoton microscopy (MPM) provided 
several advantages in comparison to single-photon confocal microscopy. 
In particular the nonlinear optics used with this technology, combined 
with the elimination of a confocal pinhole aperture, led to direct 
sectioning and the use of lower energy photons. This approach preserves 
the integrity of the observed object (i.e. tissue) thus improving 
imaging results. The technology presented here further enhances the 
capabilities of MPM by providing the following advantages:
     Increased signal-to-noise ratio.
     Enhanced image resolution due to SNR.
     Improved analytical capabilities.
     Non-contact.
     May readily be adaptable to commercial microscopes.
    Development Status: The invention is fully developed. Prototype 
microscope has been built. May need further validation by rigorous in 
vivo testing under a variety of different conditions. Also need to 
build the smaller prototype that could screw into normal objective 
turrets. Alternative realizations with `integrated optic' structures 
are also planned.
    Market: Multiphoton microscopy (MPM) has found a niche in the world 
of biological imaging as the best noninvasive means of fluorescence 
microscopy in tissue explants and living animals. Coupled with 
transgenic mouse models of disease and `smart' genetically encoded 
fluorescent indicators, its use is now increasing exponentially. 
Properly applied, it is capable of measuring calcium transients 500 
[mu]m deep in a mouse brain, or quantifying blood flow by imaging 
shadows of blood cells as they race through capillaries. One of the 
great advantages of optical microscopy is its ability to let scientists 
peek beneath the tissue surface and study cellular processes at work. 
Over the last two decades, the use of multiphoton microscopy has spread 
to all major areas of biological research. As researchers are finding 
more and more applications for this powerful technique the need for 
enhanced performance and enhanced capabilities is also increasing. The 
improvements provided in the present technology are simply added to 
existing MPM and therefore present excellent commercial opportunities.
    Inventors: Jay R. Knutson (NHLBI).

Related Publications

    1. U.S. Patent Application Publication US-2008-0063345 A1, March 
13, 2008.
    2. Presentation, 7th EBSA European Biophysics Congress, July 11-15, 
2009, Genova, Italy (http://EBSA2009.org).
    3. CA Combs, AV Smirnov, JD Riley, AH Gandjbakhche, JR Knutson, RS 
Balaban. Optimization of multiphoton excitation microscopy by total 
emission detection using a parabolic light reflector. J Micros. 2007 
Dec;228(Pt3):330-337.
    Patent Status: U.S. Provisional Application No. 61/224,772 filed 10 
Jul 2009 (HHS Reference No. E-236-2009/0-US-01).
    Related Technology: U.S. Patent Application No. 11/979,600 filed 06 
Nov 2007, now allowed (HHS Reference No. E-257-2005/0-US-04).
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, PhD, MBA; 301-435-4616; 
UR7a@nih.gov; or Michael Shmilovich, JD; 301-435-5019; 
shmilovm@mail.nih.gov.
    Collaborative Research Opportunity: The NHLBI Laboratory of 
Molecular Biophysics is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize an enhanced method of multiphoton microscopy 
that is suitable for the spectral imaging of biological samples. Please 
contact Brian W. Bailey, PhD at bbailey@mail.nih.gov for more 
information.

    Dated: December 24, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-31074 Filed 12-30-09; 8:45 am]

BILLING CODE 4140-01-P