Introduction: My group is focused on the development of X-Ray imaging techniques for clinical and research applications. In the US 72% of medical imaging procedures involve X-rays such as radiography, angiography, CT and image guided interventional procedures. We tackle two major challenges shared by these modalities, which are the lack of tissue specificity and the concern of ionizing radiation exposure. We take advantage of the wave nature of x-rays to add two new dimensions to the image contrast. These are wave scattering and refractive bending. Wave scattering reveals microscopic structures which is independent from the conventional attenuation contrast. Materials that are indistinguishable by x-ray attenuation can be separated in the scattering dimension, similar to the benefit of 2D versus 1D gel electrophoresis. Refractive bending, or phase contrast, offers the potential of significant dose reduction since it arises from the refractive index variations in the body and does not require energy absorption. Background: In 1996 S. W. Wilkins showed the first phase contrast-enhanced x-ray image with a laboratory x-ray source. In 1998 J. Clauser described a grating-based imaging system which has since been intensively developed by a number of labs. In 2007 we were the first to map wave scattering with a simple imaging method and demonstrated the ability of material separation in a 2D contrast space. In 2009 we recognized that no existing technologies were sensitive enough to provide soft tissue information without either synchrotron x-ray sources or impractical radiation doses. Our accomplishments: As a basic solution, I decided on the strategy of developing nano-metric x-ray gratings which would enable new imaging methods of high enough sensitivity to detect soft tissue structures at low radiation levels. Two major obstacles along this path are the fabrication of nano-metric x-ray gratings and imaging with only transparent phase shifting elements, since absorption gratings are impractical at this scale. Since 2012 we developed two generations of nano-metric phase gratings; discovered a universal optical effect between transparent phase masks, which underlies a high-sensitivity imaging method (PFI) using only phase gratings and compact x-ray sources; developed x-ray camera technology; invented adaptive processing algorithms; transitioned from synchrotron beamline to benchtop systems to a standalone vertical imaging system; demonstrated in mouse specimens and medical physics phantoms detection of invisible tissue structures at a fraction of clinical dose levels, which was the first time in a system outside synchrotrons. The microfabrication capabilities we built up became useful to other NHLBI labs in cell and molecular biology through collaborations. Our finding of the universal moir effect has major implications for particle beam interferometry and has been adapted by NIST Neutron Research Center for material, energy and geology research. Future plan: We entered into collaboration with the Walter Reed Medical Center Breast Imaging Center to test a prototype vertical imager for radiographic screening of breast biopsy specimens with the aim to help the subsequent pathology test to better target samples with calcifications and enable better tissue diagnosis. The IRB protocol is being reviewed by Walter Reed Medical Center. Currently the main limitation is the size of micro fabricated components. We are continually pushing the envelopes of fabrication in another project of this report, as well as instrumentation hardware and software.

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U.S. National Heart Lung and Blood Inst
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George, Alex; Chen, Peter Y; Morales-Martinez, Alejandro et al. (2017) Geometric calibration and correction for a lens-coupled detector in x-ray phase-contrast imaging. J Med Imaging (Bellingham) 4:013507
Miao, Houxun; Panna, Alireza; Gomella, Andrew A et al. (2016) A Universal Moiré Effect and Application in X-Ray Phase-Contrast Imaging. Nat Phys 12:830-834
Miao, Houxun; Chen, Lei; Mirzaeimoghri, Mona et al. (2016) Cryogenic Etching of High Aspect Ratio 400 nm Pitch Silicon Gratings. J Microelectromech Syst 25:963-967
Miao, Houxun; Gomella, Andrew A; Harmon, Katherine J et al. (2015) Enhancing Tabletop X-Ray Phase Contrast Imaging with Nano-Fabrication. Sci Rep 5:13581
Nayak, Krishna S; Nielsen, Jon-Fredrik; Bernstein, Matt A et al. (2015) Cardiovascular magnetic resonance phase contrast imaging. J Cardiovasc Magn Reson 17:71
Harmon, Katherine J; Miao, Houxun; Gomella, Andrew A et al. (2015) Motionless electromagnetic phase stepping versus mechanical phase stepping in x-ray phase-contrast imaging with a compact source. Phys Med Biol 60:3031-43
Harmon, Katherine J; Bennett, Eric E; Gomella, Andrew A et al. (2014) Efficient decoding of 2D structured illumination with linear phase stepping in X-ray phase contrast and dark-field imaging. PLoS One 9:e87127
Wen, Han; Gomella, Andrew A; Patel, Ajay et al. (2014) Boosting phase contrast with a grating Bonse-Hart interferometer of 200 nanometre grating period. Philos Trans A Math Phys Eng Sci 372:20130028
Miao, Houxun; Gomella, Andrew A; Chedid, Nicholas et al. (2014) Fabrication of 200 nm period hard X-ray phase gratings. Nano Lett 14:3453-8
Wen, Han; Wolfe, Douglas E; Gomella, Andrew A et al. (2013) Interferometric hard x-ray phase contrast imaging at 204 nm grating period. Rev Sci Instrum 84:013706

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