Production of Pulsed, Tunable, Monochromatic X-rays
 
 
CleanX-raygraph.jpg (137445 bytes)Sustained/long duration X-ray output has been demonstrated emanating from the monochromatic x-ray beamline of the Vanderbilt Free Electron Laser. Tunable, pulsed monochromatic X-rays ranging in energy from 14 - 18 keV are produced by inverse Compton scattering created by the counter propagation of the FEL e-beam and its own infrared beam. These beams are focused and optimized at an interaction zone between the linac and the wiggler where they are brought into coalignment. The X-rays produced exit the beamline through a beryllium window and are directed onto mosaic crystals which divert the beam to an imaging laboratory on the floor above the vault. The initial application of these X-rays is directed toward human imaging, specifically for the diagnosis of breast diseases including cancer. The characteristics of the X-rays are such that they can be used in standard geometry monochromatic imaging, CT like images of the breast using a rotating mosaic crystal, time-of-flight imaging and phase contrast images. Eventual extension to other portions of the body, cell biology and material sciences are already anticipated.

To see the process of X-ray production -images/Inversecomptondg.bmp

This technology is now being transferred to the commercial arena through the vehicle of a tabletop terawatt/accelerator combination. See News .

 

3-D Imaging Using A Mosaic Crystal Rotator

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Tunable, pulsed, monochromatic X-rays are now available for use in imaging. In order to take advantage of the spectral, temporal and spatial uniqueness of these beams, development of useful X-ray optics and methods for data acquisition will be required. Since differences in the linear attenuation of various tissues can be obscured using planar imaging, computed tomographic imaging is a natural extension of the first use of these X-rays. Pyrolytic graphite mosaic crystals can be used to solve many of the problems created by a geometry in which movement of the X-ray source , the patient or the detector would be impossible or highly impractical. By coupling, mosaic crystals in a rotating frame, acquiring data using CCD's and computing the final images, CT-like images of phantoms have been produced, proving the potential for this new method of evaluating tissues, humans or materials.

 

Diagram of the mosaic crystal rotator -

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Click on picture for more detail.

 

 

Collage of images obtained from 8 different angles using the mosaic crystal rotator in 45 degree increments-   

                                          Click on picture for more detail.

 

Tomographic reconstructions using the data from the collage above-

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                                                Click on picture for more detail.

 
 
 
 
Phase Contrast Imaging Using PEEM
 
 
While pulsed, tunable, monochromatic X-rays are useful for plain film radiographic procedures and acquisition of 3-D information, their utility in imaging using non-standard methodologies such as phase contrast imaging and time-resolved structural and dynamical processes has not yet been established. As a logical spin-off of the monochromatic X-ray FEL technology, we propose to bring phase contrast imaging and time-resolved imaging into the realm of X-ray microscopy using PEEM as the detector. These techniques have great relevance in both medicine and materials science. If we are to use the unique capabilities of these pulsed beams for picosecond imaging and use the small focal spot for phase contrast imaging then we must address the weak link, which has been on the detector side of the equation.
Current methods for obtaining phase contrast images consist of 60-meter distances between object and detector, Laue crystal analyzers, and X-ray interferometers, none of which is practical in a clinical setting nor outside of a synchrotron facility. We plan to modify the EM in such a way that images of materials and biological specimens can be made outside vacuum in a normal room environment using hard monochromatic X-rays. After the X-rays have traversed the object to be imaged they will, in turn, produce photoelectrons after passing through a thin X-ray transparent Beryllium window into the vacuum chamber of the EM, where they will impinge upon a photocathode. The electrons ejected from the photocathode will be amplified and focused to the microscope objective yielding spatial resolutions of from 250 Angstroms to 7 microns over a 400 by 400-micron field of view. This degree of resolution allows for close proximity detection of both refractive and diffractive wavefronts produced by variations in the refractive indices and edges within tissues or materials studied.phasevsattenbyatomicnumber.gif (114323 bytes)
This technique is being developed with an eye towards eventual use in a clinical setting. When an abnormality is detected using standard monochromatic X-ray projections, for example, further analysis of it may require biopsy by excision or needle aspiration. Any technique, which could assist in the analysis of the composition of such a lesion, could be of inestimable value, particularly if no surgical intervention would then be required. Images of both phantoms and human biopsy specimens will be made to ascertain if this technique truly delivers the 100 to 1000 X increase in information (over absorption imaging) that phase contrast imaging is theoretically capable of delivering. This type of improvement is expected, particularly in view of the fact that tissues from the body are predominantly made up of light elements. Figure at right is from Momose, Acad Radiol 1995. It shows the equivalent X-ray phase shift cross-section (p) vs. total absorption cross-section µ related to atomic number.

 

Time-of-Flight Imaging
tofdetector.png (4472 bytes)Photons that traverse the imaged part unimpeded (ballistic photons) exit the imaged volume in picoseconds. Those photons that  scatter within the tissue exit in nanoseconds. By using a fast detector that only accumulates photons for about 180 ps, one can improve the S/N ratio of the image by 6 to 9 times or alternatively reduce the radiation dose to the part by 6-9 times maintaining the same S/N in the image. Currently we are using such a detector that is sensitive to soft X-rays for early imaging research.

 

K-Edge Imaging

Since the X-rays are tunable and near-monochromatic, one can tune the output of a pulsed, tunable, monochromatic machine to the K-edge of some atom, such as iodine or gadolinium which are used in contrast materials in diagnostic radiology today. Lower doses of contrast can be given with excellent opacification of vasculature, even with intravenous doses given peripherally, making catheterization of some arteries unnecessary.
 
Protein Crystallography:

        Why travel to a synchrotron to perform crystallography, when you can have a laser synchrotron X-ray source in your own home laboratory? Since the newest version of the compact, tunable, monochromatic source is actually a tabletop, laser synchrotron X-ray source, it is a natural substitute for replacement of synchrotrons in this field.

     The technology developed by Vanderbilt and MXISystems enables performance of standard protein crystallography, MAD, Laue diffraction, powder diffraction, etc., etc., all within a widely tunable range of energies from 8-20 keV  (1.55-0.66Å) with a 0.1% – 10 % adjustable bandwidth and high flux. ( See comparison table ). The lower flux of the compact device compares favorably to the synchrotron, since researchers commonly attenuate the beam at synchrotron facilities to 1010 photons/sec. to reduce damage to their crystals while collecting data.

    Utilizing funds from the ONR grant, a protein crystallography beamline was designed, and built at the W.M. Keck Free Electron Laser Facility. This beamline consists of a MAR345 detector, a goniometer, a cryostat, and focusing X-ray optics.

    Researchers will no longer be trapped at the Cu-ka line of a standard crystallography X-ray tube in their home labs, nor are they required to travel long distances to synchrotron facilities for confirmatory studies with the ensuing delays (engendered by long lead-times for beamline availability). This will allow them to perform protein crystallography 24 hours a day/7 days a week. The X-ray beam can be focused down to 20-50 microns at the crystal, allowing one to study smaller specimens immediately upon completion of crystal growth.

    The X-ray source is also customizable to some degree for additional ease of use. Some crystallographers may not desire Laue capability, higher keV nor lower energies.

    The radiation environment around the machine and beamline is shirtsleeves. Neither heavy shielding nor a radiation vault is required.

   

In Vivo Microscopy Using Monochromatic Beams

Currently, X-ray imaging in vivo is restricted to spatial resolution on the order of .16 to .3 mm using plain films and high resolution CT, regardless of the detector used. Anatomical definition of primary functioning units of organs such as the lung, will require a new paradigm. This new mode of imaging should be painless, non-invasive, rapid, sensitive and specific. Pulsed, tunable, monochromatic X-rays offer such a probe. Since the X-ray beam is monochromatic, significant dose reduction can be achieved during imaging, while simultaneously decreasing scattered radiation, which improves conspicuity of any lesion or tissue. The tunability of the beam allows one to select the energy most suited for the task at hand. Additionally, the pulsed nature of the beam allows for time resolution of from 2-10 picoseconds.

CT microscopy using both absorption imaging and phase contrast imaging, is being developed to allow for longitudinal in vivo microscopic visualization of structures down to approximately 7 microns.

 

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